Distinct mutations leukemia. Medical search. Frequent questions

To define the mechanistic basis of clonal hematopoiesis in SDS, we investigate somatic mutations acquired by patients with SDS followed longitudinally. (nature.com)
To understand the molecular pathogenesis of MN in patients with SDS, we characterized the presence and dynamics of somatic mutations in serial, clinically annotated samples collected prospectively from patients enrolled in the North American SDS Registry and studied the functional consequences of recurrently mutated pathways. (nature.com)
Somatic mutations in in expanded T cell clones were discovered in patients with immune-mediated aplastic anemia. (helsinki.fi)
T cells with somatic mutations on JAK-STAT and MAPK pathway genes were characterized by single-cell transcriptomics. (helsinki.fi)
Leukemia-associated somatic mutations drive distinct patterns of age-related clonal hemopoiesis. (cdc.gov)
METHODS: Whole-exome sequencing was used to detect somatic mutations and large copy number variations (CNVs). (mdc-berlin.de)
However, current single-cell RNA-sequencing approaches lack the sensitivity required to reliably detect somatic mutations. (ox.ac.uk)
Relapsed acute myeloid leukemia (AML) is associated with the acquisition of additional somatic mutations which are thought to drive phenotypic adaptability, clonal selection and evolution of leukemic clones du. (biomedcentral.com)

Recent studies of acute myeloid leukemia (AML) patients have highlighted that AML may stem from alterations in how genes are expressed from DNA. (lls.org)
However, simultaneous mutation of both genes generates leukemia. (lls.org)
We also identified a set of 83 genes that were highly expressed in leukemia blasts from patients without known molecular abnormalities who subsequently relapsed following therapy. (aacrjournals.org)
As an example, Dr. Sallman has focused research and clinical trial efforts on patients who have TP53 mutation (often associated with complex genes/cytogenetics) given their high risk of transformation to acute leukemia and poor survival. (moffitt.org)
Co-expression of two mutant genes increased myeloid stem cells in animal model, suggesting that cooperation of RUNX1 and ASXL1 mutations played a critical role in leukemia transformation. (biomedcentral.com)
a AML-RMG is a capture reagent consisting of all of the exons of the genes that are currently known to be recurrently mutated in acute myeloid leukemia, based on The Cancer Genome Atlas AML study. (jamanetwork.com)
Bottom: key AML genes and pathways, showing patterns of mutations and clearance. (jamanetwork.com)
Serial VAF measurements demonstrating the clearance patterns of several recurrently mutated acute myeloid leukemia genes in the set of 50 cases. (jamanetwork.com)
FMS-like tyrosine kinase 3 ( FLT3 ) is one of the most frequently mutated genes in acute myeloid leukemia (AML). (dovepress.com)
RNA deep sequencing identified damaging mutations in both genes. (nih.gov)
The compound targets a complex of proteins that join together and turn on the genes driving the leukemia. (childrenshospital.org)
VTP-50469 disrupts two proteins in this complex, Menin and MLL, and the complex falls apart, so the leukemia genes turn off. (childrenshospital.org)
meeting both WHO-HAEM5 and ICC criteria) were younger, had higher bone marrow blast percentages and CEBPA mutation burden, infrequently harboured 2022 ELN high-risk genetic features and co-mutations in other genes, and had superior outcomes. (bvsalud.org)
Cells become cancerous by accumulating, stepwise, a series of several mutations that alter the function of genes important for cell growth. (agemed.org)
The two distinct AML1-ETO pairs share genes related to hematopoietic stem cell maintenance and cell migration suggesting that the Re leukemic stem cell-like (LSC-like) cells evolved from the Dx cells. (mdc-berlin.de)
Novel fusion genes such as ZNF384 , have been identified in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in recent years. (biomedcentral.com)
Somatic missense mutations in cancer-related genes were detected in three IHES patients. (oncotarget.com)
Our data show that a subset of IHES may be of clonal origin not related to the classical molecular aberrations of FGFR, PDGFRA/B , or T-cells, and that the initiating hits could be point mutations in a variety of genes, including spliceosome mutations or hypermethylated tumor suppressor genes. (oncotarget.com)
This is the first time that we've identified 'silencers' in leukemia or any cancer, which can shut down essential genes from long distance," Yue said. (northwestern.edu)
Many cellular signaling pathways exhibit a bowtie topology: multiple distinct signal inputs converge on a single master transcription factor, which controls the expression of downstream genes. (harvard.edu)
This process is mediated by a complex molecular machinery known as the spliceosome, which enables the production of multiple and functionally distinct proteins from single genes. (lu.se)
Overexpression of chromatin remodeling and tyrosine kinase genes in iAMP21-positive acute lymphoblastic leukemia. (cancercentrum.se)

Here we report that multiple independent somatic hematopoietic clones arise early in life, most commonly harboring heterozygous mutations in EIF6 or TP53 . (nature.com)
TP53 mutations define a maladaptive pathway with enhanced leukemic potential by inactivating tumor suppressor checkpoints without correcting the ribosome defect. (nature.com)
Subsequent development of leukemia was associated with acquisition of biallelic TP53 alterations. (nature.com)
Somatic TP53 mutations have been observed in patients with SDS who develop MDS 13 , raising the possibility that next-generation sequencing could be integrated into surveillance for somatic clones with enhanced leukemia potential. (nature.com)
However, TP53 mutations have also been identified in SDS patients without MN 14 , suggesting that additional factors must be uncovered before implementing molecular surveillance as a predictive tool in SDS. (nature.com)
Single-molecule DNA sequencing of acute myeloid leukemia and myelodysplastic syndromes with multiple TP53 alterations. (pacb.com)
Although the frequency of TP53 mutations in hemato- logic malignancies is low, these mutations have a high clinical relevance and are usually associated with poor prognosis. (pacb.com)
Somatic TP53 mutations have been detected in up to 73.3% of cases of acute myeloid leukemia (AML) with complex karyotype and 18.9% of AML with other unfavorable cytogenetic risk factors. (pacb.com)
AML with TP53 mutations, and/or chromosomal aneuploidy, has been defined as a distinct AML subtype. (pacb.com)
In low-risk myelodysplastic syndromes (MDS), TP53 mutations occur at an early disease stage and predict disease progression. (pacb.com)
TP53 mutation diagnosis is now part of the revised European LeukemiaNet (ELN) guidelines. (pacb.com)
Familial predisposition specific to leukemia is uncommon but has resulted in the identification of predisposing non-silent variants that are also observed in sporadic ALL cases, including TP53 germline mutations and low hypodiploid B-ALL, ETV6 variants and hyperdiploid ALL, and PAX5 mutations and B-ALL with dicentric/isochromosome 9. (haematologica.org)
TP53 mutations are seen in 5-10% of de novo MDS and AML, but 25-40% of therapy-related MDS and AML. (mdpi.com)
TP53 -mutated acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are among the myeloid malignancies with the poorest prognosis. (mdpi.com)

We employ mitochondrial single-cell assay for transposase-accessible chromatin with sequencing to profile 163,279 cells from 9 patients with chronic lymphocytic leukemia (CLL) collected across disease course and utilize mitochondrial DNA (mtDNA) mutations as natural genetic markers of cancer clones. (nih.gov)
This enabled identification of TFs that can be uniquely associated to the tumor cells of chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), hairy cell leukemia (HCL), and mantle cell lymphoma (MCL). (lu.se)
HCL-V affects B cells, so it's classified as a chronic lymphocytic leukemia (CLL). (healthline.com)
Methods in Molecular Biology - Chronic Lymphocytic Leukemia: Methods and Protocols , year: 2019, number of pages: 20 s. (muni.cz)
But, mutations in a different region can promote chronic lymphocytic leukemia and T cell acute lymphoblastic leukemia. (bsc.es)
Whole-genome sequencing of chronic lymphocytic leukemia identifies subgroups with distinct biological and clinical features. (ox.ac.uk)
Here, we report the whole-genome sequencing of 485 chronic lymphocytic leukemia patients enrolled in clinical trials as part of the United Kingdom's 100,000 Genomes Project. (ox.ac.uk)
While requiring independent validation, our findings highlight the potential of whole-genome sequencing to inform future risk stratification in chronic lymphocytic leukemia. (ox.ac.uk)

CML with the T315I mutation has been considered to have poor prognosis. (jcancer.org)
Acute myeloid leukemia is a hematopoietic neoplasm of dismal prognosis that results from the accumulation of immature myeloid blasts in the bone marrow and the peripheral blood. (frontiersin.org)
3-5 In this group, the presence of a DNMT3A and/or an FLT3 internal tandem duplication (ITD) mutation confers a poorer prognosis, whereas the presence of an NPM1 mutation in the absence of the aforementioned mutations is associated with an improved prognosis. (ascopost.com)
1 , 7-9 In the 2017 European Leukemia network (ELN) classification, prognosis of FLT3 -ITD mutation on the survival of AML patients was dependent on the co-occurrence of the nucleophosmin 1 gene mutation ( NPM1 mut) and the FLT3 -ITD mutation burden. (dovepress.com)
We integrated 5 independent datasets totally 665 AML patients (497 CN-AML patients) to analyzed relation between NCALD gene expression and the clinical FAB classification, gene mutation, therapy, prognosis of CN-AML. (biomedcentral.com)
The prognosis can be further stratified according to different gene mutation combinations in CN-AML patients. (biomedcentral.com)
FLT3 tyrosine kinase domain mutations are biologically distinct from and have a significantly more favorable prognosis than FLT3 internal tandem duplications in patients with acute myeloid leukemia. (ox.ac.uk)
More than 20,000 patients are diagnosed with acute myeloid leukemia (AML) in the United States annually, according to the American Cancer Society and prognosis is grim, with a five-year survival rate of only 30 percent. (northwestern.edu)

As summarized in this issue of The ASCO Post , Ivey and colleagues demonstrated that assessing for NPM1- mutated gene transcripts by reverse-transcriptase quantitative polymerase chain reaction assay is a feasible approach for measuring minimal residual disease after acute myeloid leukemia (AML) induction therapy. (ascopost.com)
Patients with NPM1 mutations or KMT2A (MLL) gene rearrangements are eligible. (childrenshospital.org)
When they introduced the second hit, a mutation in the gene NPM1 , the mice went on to develop leukemia. (childrenshospital.org)

To understand the mechanisms that mediate germline genetic leukemia predisposition, we studied the inherited ribosomopathy Shwachman-Diamond syndrome (SDS), a bone marrow failure disorder with high risk of myeloid malignancies at an early age. (nature.com)
Current surveillance strategies for patients with SDS and other leukemia predisposition syndromes rely on monitoring hematologic status by serial peripheral blood counts to identify worsening cytopenias and bone marrow examinations to identify morphologic changes or development of clonal chromosomal abnormalities 11 . (nature.com)
[ 1 , 2 ] Bone marrow and peripheral blood blast counts are strong prognostic indicators in MDS: Patients with increased blasts at diagnosis have a poorer survival, and an increasing blast count in patients already diagnosed with MDS is often a harbinger of transformation to acute myeloid leukemia ( AML ). (medscape.com)
Leukemia is a form of cancer that affects your blood cells, bone marrow, and other related tissues. (healthline.com)
Hematopoietic stem cells in the bone marrow sustain their own maintenance and give rise to "transit amplifying", lineage committed cells that terminally differentiate into distinct, mostly short-lived cell types. (mdc-berlin.de)
Mice transduced with both ASXL1 and RUNX1 mutations enhanced inhibitor of DNA binding 1 (ID1) expression in the spleen, liver, and bone marrow cells. (biomedcentral.com)
Bone marrow samples from CMML showed that ID1 overexpressed in coexisted mutations of RUNX1 and ASXL1 compared to normal control and either RUNX1 -MT or ASXL1 -MT samples. (biomedcentral.com)
Acute myelogenous leukemia (AML) is a malignant disease of the bone marrow in which hematopoietic precursors are arrested in an early stage of development. (medscape.com)

We show that germline SBDS deficiency establishes a fitness constraint that drives selection of somatic clones via two distinct mechanisms with different clinical consequences. (nature.com)
These results mechanistically link leukemia predisposition to germline genetic constraints on cellular fitness, and provide a rational framework for clinical surveillance strategies. (nature.com)
Diagnosis of leukemia predisposition provides potential opportunities for early intervention, but data to guide precision medicine approaches to clinical surveillance are lacking. (nature.com)
The 4th edition World Health Organization (WHO) classification of MDS, updated as a revised version in 2016, recognizes several distinct MDS entities with particular clinical behavior and clinicopathologic features. (medscape.com)
Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: are we ready for a prognostically prioritized molecular classification? (nature.com)
Phase I and II clinical trials) for patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) based on the underlying mutational drivers of each disease. (moffitt.org)
He has published significantly on this topic including recently in highly regarded journals including Leukemia and Haematologica and these work form the foundation of the clinical trials that he is bringing to patients in order to improve their quality of life and survival. (moffitt.org)
With spatial tissue analysis, we demonstrate that the intratumoral and peritumoral regions of ccRCC patients represent distinct immunological profiles and are associated with clinical phenotypes. (helsinki.fi)
The BRAF mutation status cannot be predicted based on clinical parameters and outcome analysis showed no difference. (oncotarget.com)
Acute myeloid leukemia (AML) is a heterogeneous disease in terms of genetic basis, clinical, biological and prognostic, and is a malignant clonal disease of leukemia stem cells (LSCs). (biomedcentral.com)
This paper reviewed the latest advances in BRAF gene mutation associated with ameloblastoma and its potential clinical significance. (wanfangdata.com.cn)
The novel finding that biologically distinct activating mutations of the same gene can be associated with markedly different clinical outcomes has implications for risk stratification and therapy and is significant to the understanding of chemoresistance in AML. (ox.ac.uk)
The restoration of pathogenic chromatin structure warrants further investigation into the targeted clinical usage of the existing drugs that could manipulate DNA methylation in myelodysplastic syndromes or leukemia," Yue added. (northwestern.edu)
We demonstrate the relationship of these features with clinical outcome and show that integration of 186 distinct recurrent genomic alterations defines five genomic subgroups that associate with response to therapy, refining conventional outcome prediction. (ox.ac.uk)
The identification of specific mutations is of immediate clinical importance by providing improved diagnostic precision and opportunities for prognostic evaluation. (lu.se)

Emergence of LSC is dependent on individual or combined genetic mutations that broadly determine the cellular affiliation of the leukemia, and permit or impose ectopic self-renewal and a restricted differentiation potential into what constitutes the proliferative bulk of the leukemia ( 5 , 6 ). (frontiersin.org)
As cancer care has grown more sophisticated, we have developed many targeted therapies that work against specific genetic mutations in cancer cells. (mdanderson.org)
We identify an extended catalog of recurrent coding and noncoding genetic mutations that represents a source for future studies and provide the most complete high-resolution map of structural variants, copy number changes and global genome features including telomere length, mutational signatures and genomic complexity. (ox.ac.uk)

Previously, we observed that transcription factor RUNX1 mutations ( RUNX1 -MT) coexisted with ASXL1 -MT in CMML and at myeloid blast phase of chronic myeloid leukemia. (biomedcentral.com)
The contribution of RUNX1 mutations in the pathogenesis of myeloid transformation in ASXL1 -mutated leukemia, however, remains unclear. (biomedcentral.com)
At 9 months post-BMT, mice harboring combined RUNX1 and ASXL1 mutations developed disease characterized by marked splenomegaly, hepatomegaly, and leukocytosis with a shorter latency. (biomedcentral.com)
The present study demonstrated the biological and functional evidence for the critical role of RUNX1 -MT in ASXL1 -mutated leukemia in the pathogenesis of myeloid malignancies. (biomedcentral.com)
RUNX1-positive leukemia cells in preclinical models. (lu.se)
Germline mutations in the gene AML1 ( RUNX1, CBFA2 ) occur in the familial platelet disorder with predisposition for AML, an autosomal dominant disorder characterized by moderate thrombocytopenia, a defect in platelet function, and propensity to develop AML. (medscape.com)

In order to understand why these mutations frequently overlap in AML patients, the team expressed both mutations in normal blood stem cells. (lls.org)
Chronic myeloid leukemia (CML) is a clonal expansion of the progenitor hematopoietic stem cells arising from the existence of the fusion BCR-ABL oncogene, that represents 15%-20% of the newly diagnosed cases of leukemia patients [ 1 - 2 ]. (jcancer.org)
Akin to the normal hematopoietic system, leukemias are sustained by a small number of leukemia stem-like cells (LSC), which can be distinct from the normal hematopoietic stem cells (HSC) but also exhibit functional characteristics of self-renewal and (abnormal or hindered) differentiation, and are often quiescent ( 2 - 4 ). (frontiersin.org)
Jude CD, Gaudet JJ, Speck NA, Ernst P. Leukemia and hematopoietic stem cells: balancing proliferation and quiescence. (nature.com)
Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia. (ox.ac.uk)
are a group of clonal hematopoietic stem cell disorders unified by the presence of distinct mutations of hematopoietic stem cells. (msdmanuals.com)
Splicing factor mutations are particularly prevalent in MDS, a group of heterogeneous hematological disorders characterized by defective blood stem cells and a high risk of leukemia development. (lu.se)

The researchers worked with mice that had the first hit, a mutation in the gene DNMT3A that is associated with CHIP. (childrenshospital.org)
These differences appear to have significant molecular implications, exemplified by a DNMT3A/FLT3-ITD patient where the leukemia switched from an AP-1 regulated clone at Dx to a mTOR signaling driven clone at Re. (mdc-berlin.de)

Survival of patients with SDS who develop myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) is poor 10 . (nature.com)
Dr. Sallman's research focuses on the development of novel, targeted therapeutic strategies for patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). (moffitt.org)
Cases previously classified as erythroid/myeloid subtype, based on the 2008 WHO classification, are currently categorized either as myelodysplastic syndrome with excess blasts or acute myeloid leukemia, not otherwise specified. (medscape.com)
Our results showed that a mutation of C/EBPα in one allele was observed in AML after myelodysplastic syndrome, while the 2 alleles are mutated in de novo AML. (elsevierpure.com)
Researchers at Lund University Faculty of Medicine have determined a novel mechanism linking the metabolism of ribonucleic acids, RNA, to the development of leukemia in myelodysplastic syndrome patients, MDS. (lu.se)

BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous and aggressive blood cancer that results from diverse genetic aberrations in the hematopoietic stem or progenitor cells (HSPCs) leading to the expansion of blasts in the hematopoietic system. (mdc-berlin.de)
The current approach to classifying leukemia is based on the 2016 World Health Organization (WHO) system ( classification for hematopoietic neoplasms ). (msdmanuals.com)

SDS is predominantly caused by biallelic germline mutations in the SBDS gene 5 . (nature.com)

Recently, the identification of recurrent gene mutations in AML has helped refine AML prognostication, especially for patients with intermediate-risk disease. (ascopost.com)
In recent years, recurrent MAPK signaling mutations were identified in ameloblastoma, among which BRAF-V600E is the most prominent type. (wanfangdata.com.cn)
Identification of recurrent SMO and BRAF mutations in ameloblastomas [J].2014,46(7). (wanfangdata.com.cn)
Recurrent BRAF mutations in Langerhans cell histiocytosis. (wanfangdata.com.cn)

Although mutation- or pathway-directed targeted therapy (e.g., using tyrosine kinase inhibitors to treat Philadelphia chromosome [Ph]-positive and Phlike B-cell-ALL) is currently available for only a minority of children with ALL, many of the newly identified molecular alterations have led to the exploration of approaches targeting deregulated cell pathways. (haematologica.org)
We study the development of blood cells and the emergence of leukemia by focusing on the molecular genetics of self-renewal and its connection to differentiation into functional cells of the innate immune system, like macrophages, granulocytes, and dendritic cells. (mdc-berlin.de)
Additional sex combs-like 1 ( ASXL1 ) mutations have been described in all forms of myeloid neoplasms including chronic myelomonocytic leukemia (CMML) and associated with inferior outcomes, yet the molecular pathogenesis of ASXL1 mutations ( ASXL1 -MT) remains poorly understood. (biomedcentral.com)
Acute myeloid leukemia (AML) is a severe heterogeneous group of neoplastic disorders driven by several molecular alterations. (dovepress.com)
Thus, 2 types of C/EBPα mutations are implicated in leukemogenesis, involving different and cooperating molecular mechanisms. (elsevierpure.com)
Specific and straightforward molecular investigation of ß-thalassemia mutations in the Malaysian Malays and Chinese using direct TaqMan genotyping assays. (cdc.gov)
Our study indicates that in-frame bZIP CEBPA mutations are the critical molecular aberrations associated with favorable outcomes in AML patients treated with curative intent chemotherapy. (bvsalud.org)
We applied this technique to analyze more than 2,000 SCs from patients with chronic myeloid leukemia (CML) throughout the disease course, revealing heterogeneity of CML-SCs, including the identification of a subgroup of CML-SCs with a distinct molecular signature that selectively persisted during prolonged therapy. (ox.ac.uk)
Although, molecular genetic analyses became more and more important to guide therapy decisions in leukemia, banding cytogenetic analysis has retained its vital role in diagnosis and monitoring of chronic myelo. (biomedcentral.com)
Therefore, it is crucial to understand how those subtype-defining mutations give rise to the leukemia cell phenotype through changing the chromatin 3D structure," said Yue, who is also a professor of Biochemistry and Molecular Genetics , of Pathology and director of the Center for Cancer Genomics at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. (northwestern.edu)

Interestingly, these studies show that AML patients are unique amongst other cancers in that they frequently harbor mutations in the "epigenome" and "RNA splicing," which are part of the cellular machinery that regulates which proteins are ultimately expressed in the cell. (lls.org)
In the old days, we thought that cancers were made of many identical cells, all with the same features and mutations. (mdanderson.org)
Mutations in certain regions of NOTCH1 cause it to act as a tumor suppressor in lung, skin and head and neck cancers. (bsc.es)
See Chronic Leukemias: 4 Cancers to Differentiate , a Critical Images slideshow, to help detect chronic leukemias and determine the specific type present. (medscape.com)

Experimental hematology, leukemia research, in combination with stem cell research strives to untangle the underlying "grammar" of transcription factor networks. (mdc-berlin.de)
Methods: The Leukemia and Lymphoma Committee of the Japanese Society of Pediatric Hematology and Oncology (JSPHO) sent out questionnaires to 110 JSPHO affiliated hospitals and collected cases of MNPKL diagnosed during the period 2000-2013. (confex.com)

For a growing number of tumors the BRAF V600E mutation carries therapeutic relevance. (oncotarget.com)
High frequency of BRAF V600E mutations in ameloblastoma [J].2014,232(5). (wanfangdata.com.cn)

Here, we determined the effect of Jiyuan oridonin A (JOA), an ent -kaurene diterpenoid compound, on the differentiation blockade in imatinib-sensitive, particularly, imatinib-resistant CML cells with BCR-ABL-T315I mutation by cell proliferation assay, apoptosis analysis, cell differentiation analysis, cell cycle analysis and colony formation assay. (jcancer.org)
We found that JOA at lower concentration significantly inhibited the proliferation of CML cells expressing mutant BCR-ABL (T315I mutation included) and wild-type BCR-ABL, which was due to that JOA induced the cell differentiation and the cell cycle arrest at G0/G1 phase. (jcancer.org)

Different subtypes of AML are driven by these distinct genomic mutations, which creates a roadblock for treatment - patients with different subtypes can respond differently to the same therapy. (northwestern.edu)
Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes. (who.int)
Soft tissue tumors (STT) constitute a heterogeneous group of approximately 100 distinct neoplasms, including more than 50 malignant subtypes, so-called sarcomas. (lu.se)

Dr. Abdel-Wahab's team demonstrates that a likely contributor to leukemogenesis caused by mutations in both SRSF2 and IDH2 is a reduction in a transcriptional regulator called INTS3. (lls.org)
Moreover, C/EBPα-C m strongly blocked myeloid differentiation of 32Dcl3 cells, suggesting its class II mutation-like role in leukemogenesis. (elsevierpure.com)

d Targeted Ampliseq is a polymerase chain reaction-based digital sequencing approach that allows for accurate determination of the frequency of specific mutations in acute myeloid leukemia samples. (jamanetwork.com)

In the pyridoxine-responsive subtype, point mutations on the X chromosome have been identified that result in a δ-amino levulinic acid synthase (ALAS-2) with very low enzymatic activity. (medscape.com)

Both tumor entities harboring FLT3-ITDs or IDH1 mutations showed a more complex composition of cell types along the myeloid differentiation trajectory than MLL fusions. (uni-heidelberg.de)
CONCLUSIONS: In summary, the single cell RNA data underpinned the tumor heterogeneity not only amongst patient blasts with similar initiating mutations but also between each Dx-Re pair. (mdc-berlin.de)

We observe stable propagation of mtDNA mutations over years in the absence of strong selective pressure, indicating clonal persistence, but dramatic changes following tight bottlenecks, including disease transformation and relapse posttherapy, paralleled by acquisition of copy-number variants and changes in chromatin accessibility and gene expression. (nih.gov)
Furthermore, we link CLL subclones to distinct chromatin states, providing insight into nongenetic sources of relapse. (nih.gov)
Analysis from scRNA and scATAC V showed different FLT3 activity/chromatin signatures within clusters of leukemic cells in the relapse that could be explained by midostaurin resistance and the emergence of distinct subclones as detected by scDNA-seq. (uni-heidelberg.de)
Relapse risk following truncation of PEG-asparaginase in childhood acute lymphoblastic leukemia. (cancercentrum.se)
ÓG, Vaitkeviciene G, Lepik K, Forslund A, Heyman M, Harila-Saari A. Impact of body mass index on relapse in children with acute lymphoblastic leukemia treated according to Nordic treatment protocols. (cancercentrum.se)

However, they made the unexpected discoveries that these SRSF2 mutations are more common than previously anticipated in AML and that mutations in SRSF2 commonly overlap with mutations in a protein called IDH2. (lls.org)
Mutations in either SRSF2 or IDH2 lead to alterations in normal blood stem cell function but do not lead to leukemia. (lls.org)
The team therefore demonstrates that IDH2-induced changes to the epigenome alter SRSF2-induced RNA splicing in a way that drives the development of leukemia. (lls.org)
The team looked at splicing in a type of brain cancer called glioma, where many patients have mutations in IDH2 and the related protein IDH1. (lls.org)

Panels A through D show examples of different patterns of clearance of leukemia-associated mutations after induction therapy in 4 acute myeloid leukemia cases. (jamanetwork.com)
Whole-exome sequencing and genome-wide methylation analyses identify novel disease associated mutations and methylation patterns in idiopathic. (oncotarget.com)
Patients with acute myeloid leukemia, the most common type of adult blood cancer, show large-scale genomic mutations and altered DNA folding patterns that could help identify potential therapeutic targets, according to a Northwestern Medicine study published in Nature . (northwestern.edu)
These mutations were associated with unique DNA folding patterns, or chromatin "loops" in AML cells. (northwestern.edu)

Treatment with the IDH1 inhibitor revealed a partially reversible pattern of accessibility while other mutation-induced epigenetic modifications could not be reverted. (uni-heidelberg.de)

JOA displayed the activity of inhibiting the BCR-ABL and promoted differentiation of not only imatinib -sensitive but also imatinib -resistant cells with BCR-ABL mutation, which could become a potent lead compound to overcome the imatinib -resistant induced by inhibitors of BCR-ABL tyrosine kinase in CML therapy. (jcancer.org)
The treatment paradigm of AML patients harboring FLT3 mutations (30%) has been modified by the discovery of tyrosine kinase inhibitors. (dovepress.com)
The prognostic impact of tyrosine kinase domain (TKD) mutations of the fms-like tyrosine kinase-3 (FLT3) gene in acute myeloid leukemia (AML) is currently uncertain. (ox.ac.uk)

Sub-gene algorithms provide a high-resolution view that can explain why different mutations in the same gene can lead to distinct phenotypes, depending on how the mutation impacts specific protein regions. (bsc.es)
Figure: Three cancer mutation groups in the protein PIK3CA identified by different subgene algorhytms. (bsc.es)
Selective shRNA knockdown identified ribosomal protein L39 (RPL39) and myeloid leukemia factor 2 (MLF2) as the top candidates that affect BCSC self-renewal. (nih.gov)
Two types of mutations of a transcription factor CCAAT-enhancer binding protein α (C/EBPα) are found in leukemic cells of 5%-14% of acute myeloid leukemia (AML) patients: N-terminal mutations expressing dominant negative p30 and C-terminal mutations in the basic leucine zipper domain. (elsevierpure.com)
Functional studies indicated that these mutations alter the stability of LIFR messenger RNA transcripts, resulting in the absence of the LIFR protein and in the impairment of the JAK/STAT3 signaling pathway in patient cells. (tau.ac.il)
BRAF gene mutations lead to continuous activation of the mitogen-activatd protein kinase (MAPK) pathway, which resulting in abnormal cell proliferation and tumorigenesis. (wanfangdata.com.cn)
Scope includes mutations and abnormal protein expression. (cancerindex.org)

AML can present as different combinations of genomic mutations in different patients. (northwestern.edu)
In the current study, Yue and colleagues used deep sequencing and whole-genome sequencing techniques to analyze blood samples from patients with and without AML, finding that patients with AML harbored large-scale genomic mutations. (northwestern.edu)

Researchers and clinicians can develop personalized medicines and improve diagnosis by identifying the biomarkers associated with mutations. (mdpi.com)

Previously, we have shown that dysregulation of the WNT-signaling pathway and interference with the transcription factor IRF8 are major deregulated pathways in chronic myelogenous leukemia (CML). (mdc-berlin.de)

To characterize gene expression signatures in acute lymphocytic leukemia (ALL) cells associated with known genotypic abnormalities in adult patients. (aacrjournals.org)
Nearly half of adult AML patients exhibit a cytogenetic normal acute myeloid leukemia (CN-AML). (biomedcentral.com)
BRAF(V599E) Mutation Is the Leading Genetic Event in Adult Sporadic Papillary Thyroid Carcinomas. (wanfangdata.com.cn)
It also turns out that more common adult leukemias are using these same mechanisms," says Armstrong. (childrenshospital.org)

Hofvander J, Jo VY, Fletcher CDM, Puls F, Flucke U, Nilsson J, Magnusson L, Mertens F. PHF1 fusions cause distinct gene expression and chromatin accessibility profiles in ossifying fibromyxoid tumors and mesenchymal cells. (lu.se)

After more than four decades of intensive research, the cellular origins of acute lymphocytic leukemia (ALL) have been well defined, and several distinct genetic mechanisms that lead to malignant transformation of these cells have been identified ( 1 - 4 ). (aacrjournals.org)

BRAF p.V600E mutations are not unique to ameloblastoma and are shared by other odontogenic tumors with ameloblastic morphology. (wanfangdata.com.cn)

Single-cell multi-omic profiling of CLL reveals the utility of somatic mtDNA mutations as in vivo barcodes, which mark subclones that can evolve over time along with changes in accessible chromatin and gene expression profiles to capture dynamics of disease evolution. (nih.gov)

Activity of these inhibitors depends on their mechanism of receptor binding (active vs inactive conformation) and efficacy against the FLT3-ITD and -TKD mutations (type 1 inhibitors are active both on FLT3 -ITD and TKD, whereas type 2 inhibitors are active only on FLT3 -ITD). (dovepress.com)
Although the impact of FLT3 -ITD mutation is unclear in the context of venetoclax-azacitidine treatment, 6 the negative impact of FLT3 -ITD on survival of AML patients treated with ICT is well established. (dovepress.com)
001). In multivariate analysis, impact of FLT3/TKDs on OS when including all mutant-positive patients was not significant, but patients with high-level mutations (more than 25% mutant) had a significantly improved outcome (P = .004). (ox.ac.uk)

the virus had a missense mutation in the preponderant surface glycoprotein called gE ( 1 , 2 ). (cdc.gov)

39 (48%) patients met WHO-HAEM5 criteria for AML with CEBPA mutation, among which 30 (77%) had biallelic CEBPA mutations and 9 (23%) had a single bZIP mutation. (bvsalud.org)

Mutations in these key transcription factors dysregulate hematopoiesis and cause diseases, such as leukemia and immune defects. (mdc-berlin.de)
These mutations disrupt proper cell functioning, including the organization of chromatin 3D structures that regulate cell replication, differentiation and transcription. (northwestern.edu)

[ 3 ] The 2016 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia continued to recognize pure erythroid leukemia but eliminated the erythroid/myeloid type of acute erythroleukemia. (medscape.com)
MNKPL is classified as mixed phenotype acute leukemia, and not otherwise speciﬁed rare types (MPAL NOS rare types) in WHO classification. (confex.com)
AML with CEBPA mutation and AML with in-frame bZIP CEBPA mutations define favorable-risk disease entities in the proposed 5th edition of the World Health Organization Classification (WHO-HAEM5) and the International Consensus Classification (ICC), respectively. (bvsalud.org)
In 1988, ALCL was added as a distinct entity to the revised Kiel classification, and in 1994, it was included in the Revised European-American Lymphoma (REAL) classification. (medscape.com)

In acute myeloid leukemia (AML), initiation of tumorigenesis via multiple oncogenic mutations occurs throughout various stages of hematopoiesis that disrupt the corresponding transcriptomic and epigenetic profiles. (uni-heidelberg.de)
The idea is that you would screen people and follow those who have clonal hematopoiesis, and treat people who develop the second mutation," says Armstrong. (childrenshospital.org)

What is Hairy Cell Leukemia-Variant (HCL-V)? (healthline.com)
Hairy cell leukemia-variant is an extremely rare and unique type of leukemia (cancer) that was once grouped with another type but is now considered a separate condition. (healthline.com)
One rare form of leukemia is hairy cell leukemia (HCL) , named for the hair-like filaments found on affected white blood cells. (healthline.com)
Hairy cell leukemia-variant (HCL-V) was once thought to be a form of HCL but is now viewed as a distinct condition. (healthline.com)
What causes hairy cell leukemia-variant? (healthline.com)
What are the symptoms of hairy cell leukemia-variant? (healthline.com)
How do doctors diagnose hairy cell leukemia-variant? (healthline.com)
How is hairy cell leukemia-variant treated? (healthline.com)
What is the survival rate of hairy cell leukemia-variant? (healthline.com)
BRAF mutations in hairy-cell leukemia. (wanfangdata.com.cn)

While for most LCH-patients efficient therapies are available, patients with BRAF mutations may benefit from the BRAF inhibitor vemurafenib. (oncotarget.com)

mtDNA mutations thus mirror disease history and provide naturally occurring genetic barcodes to enable patient-specific study of cancer subclonal dynamics. (nih.gov)
It's a chronic form of leukemia, meaning it's typically a more slowly developing form of the disease. (healthline.com)
Through studying a series of 19 families with SWS/SJS2, we have mapped the disease gene to chromosome 5p13.1 at locus D5S418 (Z max = 10.66 at θ = 0) and have identified null mutations in the leukemia inhibitory factor receptor (LIFR or gp190 chain) gene. (tau.ac.il)

We sought to assess the differences between the ICC and WHO-HAEM5 for AML with CEBPA mutation. (bvsalud.org)
81 (11%) AML patients had CEBPA mutations. (bvsalud.org)
Compared to patients only meeting WHO-HAEM5 criteria, patients with in-frame bZIP CEBPA mutations (ie. (bvsalud.org)

Erythroleukemia is a subtype of acute myeloid leukemia ( AML ) that is distinguished by erythroblastic proliferation. (medscape.com)

Chronic myeloid leukemia (CML) results from BCR-ABL oncogene, which blocks CML cells differentiation and protects these cells from apoptosis. (jcancer.org)
Recent study showed that iASPP could impact the proliferation and apoptosis of leukemia cells by interacting with FHL2 . (nature.com)
FHL2 interacts with iASPP and impacts the biological functions of leukemia cells. (nature.com)
Leukemias affecting these cells are called myeloid leukemias. (healthline.com)
The exact causes of CLLs aren't known, but experts believe that genetic changes - called mutations - can cause your B cells to multiply too often. (healthline.com)
Key gene regulatory proteins control cell multiplication and instruct cells to adopt distinct cell fates. (mdc-berlin.de)
Dysregulation of these master switches may affect differentiation, which can lead to "confused" cells as the potential progenitors of leukemia. (mdc-berlin.de)
there are distinct groups of cancer cells within a patient. (mdanderson.org)
The leukemic cells in erythroleukemia often carry complex karyotypes and mutations in oncogenes known to be associated with AML. (medscape.com)
Proof of antiviral clonal T-cells in leukemia patients during TKI therapy. (helsinki.fi)
These powerful data-sifting tools are helping untangle the complexity of cancer, and find previously unidentified mutations that are important in creating cancer cells. (bsc.es)
These mutations are somatic, which means they are acquired during a person's lifetime and are present only in certain cells. (medlineplus.gov)
Researchers have found a translocation that attaches this region of chromosome 10 to part of chromosome 16 in some people with a cancer of blood-forming cells called acute myeloid leukemia (AML). (medlineplus.gov)
As we age, many of us acquire a mutation that enables certain of our blood cells to multiply faster than others, forming their own distinct population. (childrenshospital.org)
But if a second hit comes that makes those cells malignant, "it's essentially a guarantee you will get leukemia in the not-too-distant future," says Scott Armstrong, MD, PhD , president of the Dana-Farber/Boston Children's Cancer and Blood Disorders Center . (childrenshospital.org)
But if these mice were treated early with a compound called VTP-50469, the premalignant blood cells stopped multiplying and leukemia never developed. (childrenshospital.org)
We eradicated the cells that would ultimately become leukemia cells," says Armstrong. (childrenshospital.org)
In the infant leukemia study, done in mice and leukemia cell lines, VTP-50469 treatment led to sharp decreases in the number of leukemia cells, and, in some animals, remission of the cancer. (childrenshospital.org)
Leukemia is a malignant condition involving the excess production of immature or abnormal leukocytes, which eventually suppresses the production of normal blood cells and results in symptoms related to cytopenias. (msdmanuals.com)
Chronic leukemias have more mature cells than do acute leukemias. (msdmanuals.com)

With Prof. Eva Hellström-Lindberg's group at the Karolinska Institute, Maciej Cieśla and coworkers discovered dynamic regulation of SF3B1 levels during the malignant transformation from MDS to leukemia. (lu.se)

DNA methylation and copy number variation profiling of T-cell lymphoblastic leukemia and lymphoma. (cancercentrum.se)

Within B-lineage ALL, distinct signatures were associated with ALL1/AF4 and E2A/PBX1 gene rearrangements. (aacrjournals.org)
The trial began in adults and is now open to children as young as 1 month of age with relapsed or refractory acute leukemia (ALL, AML, or mixed lineage). (childrenshospital.org)

Anatomy21

Organisms17

Diseases43

Chemicals and Drugs52

Analytical, Diagnostic and Therapeutic Techniques and Equipment36

Phenomena and Processes88

Disciplines and Occupations1

Information Science5

Named Groups1

Health Care9

Publication Characteristics1

Somatic mutations8

Genes22

TP5314

Chronic lymphocy8

Prognosis8

NPM13

Bone marrow8

Clinical15

Genetic mutations3

RUNX16

Stem cells7

DNMT3A2

Myelodysplastic5

Hematopoietic2

Germline mutations1

Recurrent4

Molecular10

Cancers4

Hematology2

BRAF V600E2

Cell differentiation2

Subtypes3

Leukemogenesis2

Specific mutations1

Point mutations1

Tumor2

Relapse5

IDH24

Patterns4

IDH11

Tyrosine kinase3

Protein7

Genomic2

Diagnosis1

Pathways1

Adult4

Chromatin Accessibility1

Lymphocytic1

Tumors1

Gene expression1

FLT33

Missense1

Biallelic1

Transcription2

Classification4

Hematopoiesis2

Hairy cell leu10

Inhibitor1

Disease3

CEBPA3

Subtype1

Cells20

Malignant1

Methylation1

Lineage2