Constitutively leukemia myelogenous chronic bcr abl positive. Medical search. Frequent questions

In CML, the gene is activated by being translocated within the BCR (breakpoint cluster region) gene on chromosome 22. (wikipedia.org)
Approximately 95% of all CML patients harbor the gene fusion, BCR-ABL, which is formed via a double stranded break (DSB) within both the Abelson oncogene 1 (ABL) on chromosome 9q, which codes for a non-receptor tyrosine kinase (ABL), and the breakpoint cluster region gene (BCR) on chromosome 22q. (ubc.ca)
In chronic myelogenous leukemia (CML) patients, an aberrant translocation results in the replacement of the first exon of Abl with the BCR (breakpoint cluster region) gene. (umbc.edu)
In chronic myelogenous leukemia, the Philadelphia chromosome leads to a fusion protein of abl with bcr (breakpoint cluster region), termed bcr-abl. (keralapharmacist.com)

Dasatinib (Sprycel): Indicated for the treatment of adult patients with chronic myeloid leukemia in chronic, accelerated, or myeloid or lymphoid blast phase who are resistant or intolerant to prior therapy including imatinib. (medscape.com)
The Tel-ARG fusion protein, resulting from reciprocal translocation between chromosomes 1 and 12, is associated with acute myeloid leukemia (AML). (umbc.edu)
The therapeutic approach to the patient with acute myeloid leukemia (AML) currently evolves toward new frontiers. (ashpublications.org)
The term acute myeloid leukemia (AML) collectively refers to a mixture of distinct diseases that differ with regard to their pathogenetic evolution, genetic abnormalities, clinical features, response to therapy, and prognosis. (ashpublications.org)
Chronic myeloid leukemia (CML) is a myeloproliferative disease caused due to translocation between chromosome 9 and 22 leading to a chimeric gene product known as Bcr-Abl. (eurekaselect.com)
Holyoake, T.L. A comparison of normal and leukemic stem cell biology in chronic myeloid leukemia. (eurekaselect.com)
Acute myeloid leukemia (AML) patients with a high allelic burden of an internal tandem duplication ( ITD )-mutated FMS - like Tyrosine Kinase - 3 ( FLT3 ) have a dismal outcome. (biomedcentral.com)
Acute myeloid leukemia (AML) is mainly a fatal disease. (biomedcentral.com)
To identify regulators of primitive chronic myeloid leukemia (CML) cells, we performed a high-content cytokine screen using primary CD34 + CD38 low chronic phase CML cells. (haematologica.org)
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm caused by an acquired 9;22-chromosomal translocation in a hematopoietic stem cell (HSC) resulting in the expression of the BCR-ABL1 fusion protein. (haematologica.org)
7 In CML and acute myeloid leukemia (AML), we and others have shown that IL-1 is a positive regulator of LSC, and blocking IL-1 signaling inhibits the LSC. (haematologica.org)
Acute Myeloid Leukemia (AML) is an aggressive hematological malignancy that relies on highly heterogeneous cytogenetic alterations. (mdpi.com)
Constitutively activating internal tandem duplications (ITD) of FLT3 (FMS-like tyrosine kinase 3) are the most common mutations in acute myeloid leukemia (AML) and correlate with poor prognosis. (ashpublications.org)
FLT3 is frequently mutated in patients with acute myeloid leukemia (AML), which correlates with poor prognosis and decreased patient survival. (ashpublications.org)
This mechanism also applies to hematopoietic cells transformed by other HOX genes, including CDX2, which is highly expressed in a majority of acute myeloid leukemias, thus providing a molecular approach based on GSK-3 inhibitory strategies to target HOX-associated transcription in a broad spectrum of leukemias. (stanford.edu)
Chronic Myeloid Leukemia (CML) is a stem cell disease sustained by a rare population of quiescent cells which are to some extent resistant to tyrosine kinase inhibitors (TKIs). (oncotarget.com)
In addition, the BCR-ABL fusion gene product, a constitutively activated tyrosine kinase which is crucial for the development of chronic myeloid leukemia (CML), is highly sensitive to bosutinib. (mdm2-receptor.com)

BCR-ABL encodes a constitutively active tyrosine kinase BCR-ABL responsible for the uncontrolled proliferation associated with chronic myelogenous leukemia. (ubc.ca)
Bcr-Abl fusion protein has constitutively activated Abl tyrosine kinase activity which is responsible for the uncontrolled proliferation in CML The tyrosine kinase inhibitors (TKIs) such as Imatinib, Dasatinib, and Nilotinib are the current first-line treatments approved by the United States Food and Drug Administration (US FDA) for the treatment of the disease. (eurekaselect.com)

It may be a critical substrate for p210(bcr/abl), a chimeric protein whose presence is associated with CML. (novusbio.com)
Acute leukemias induced by MLL chimeric oncoproteins are among the subset of cancers distinguished by a paradoxical dependence on GSK-3 kinase activity for sustained proliferation. (stanford.edu)

The Bcr-Abl protein induces the upregulation of proto-oncogene c-Jun, which is involved in Bcr-Abl transforming activity in Bcr-Abl positive cells. (tmu.edu.tw)
For example, the diagnostic hallmark of chronic myelogenous leukemia (CML) is an oncogene fusion formed from a reciprocal translocation (t(9;22)(q34.1;q11.2)) between chromosomes 9 and 22 that results in an altered chromosome 22q known as the Philadelphia chromosome. (ubc.ca)
Imatinib is specific for the TK domain in abl (the Abelson proto-oncogene), c-kit and PDGF-R (platelet-derived growth factor receptor). (keralapharmacist.com)
Witte, O.N. Tyrosine kinase activity and transformation potency of bcr-abl oncogene products. (eurekaselect.com)
Stone, M. Translocation of C-Abl oncogene correlates with the presence of a philadelphia chromosome in chronic myelocytic leukaemia. (eurekaselect.com)
BCR-ABL oncogene activates multiple cross-talking signal transduction pathways (STP), such as RAS/MEK/ERK, PI3K/Akt, Wnt and STAT5, contributing to abnormal proliferation of clonal cells. (oncotarget.com)

Mutations in the ABL1 gene are associated with chronic myelogenous leukemia (CML). (wikipedia.org)
This fact explains why many BCR-ABL mutations can cause resistance to imatinib by shifting its equilibrium toward the open or active conformation. (keralapharmacist.com)
The Bcr-Abl point mutations, including the gatekeeper T315I mutations, are the principal cause for the development of resistance to TKIs. (eurekaselect.com)
Remarkably, bosutinib has been found to be capable of overcoming the majority of IM-resistant BCR-ABL mutations. (mdm2-receptor.com)

Tyrosine-protein kinase ABL1 also known as ABL1 is a protein that, in humans, is encoded by the ABL1 gene (previous symbol ABL) located on chromosome 9. (wikipedia.org)
The BCR-ABL protein can be inhibited by various small molecules. (wikipedia.org)
Docking protein 1 is constitutively tyrosine phosphorylated in hematopoietic progenitors isolated from chronic myelogenous leukemia (CML) patients in the chronic phase. (novusbio.com)
The resulting BCR-Abl fusion protein is constitutively active and associates into tetramers, resulting in a hyperactive kinase sending a continuous signal. (umbc.edu)
Imatinib works by binding close to the ATP binding site of bcr-abl, locking it in a closed or self-inhibited conformation, and therefore inhibiting the enzyme activity of the protein semi-competitively. (keralapharmacist.com)
Imatinib also inhibits the abl protein of non-cancer cells but cells normally have additional redundant tyrosine kinases which allow them to continue to function even if abl tyrosine kinase is inhibited. (keralapharmacist.com)
1 The BCR-ABL1 fusion protein is a constitutively active tyrosine kinase and triggers a cascade of aberrant downstream signaling pathways leading to clonal outgrowth of CML cells and subsequent disease manifestation. (haematologica.org)
We demonstrate here that GSK-3 maintains the MLL leukemia stem cell transcriptional program by promoting the conditional association of CREB and its coactivators TORC and CBP with homedomain protein MEIS1, a critical component of the MLL-subordinate program, which in turn facilitates HOX-mediated transcription and transformation. (stanford.edu)

c-Abl is sometimes used to refer to the version of the gene found within the mammalian genome, while v-Abl refers to the viral gene, which was initially isolated from the Abelson murine leukemia virus. (wikipedia.org)
Abl2, also known as ARG (Abelson-related gene), is thought to play a cooperative role with Abl in the proper development of the nervous system. (umbc.edu)

Huang, HM & Liu, JC 2009, ' c-Jun blocks cell differentiation but not growth inhibition or apoptosis of chronic myelogenous leukemia cells induced by STI571 and by histone deacetylase inhibitors ', Journal of Cellular Physiology , vol. 218, no. 3, pp. 568-574. (tmu.edu.tw)
In response to DNA damage or oxidative stress, Abl is transported to the nucleus where it induces apoptosis. (umbc.edu)
Like all tyrosine-kinase inhibitors, imatinib works by preventing a tyrosine kinase enzyme, in this case BCR-Abl, from phosphorylating subsequent proteins and initiating the signaling cascade necessary for cancer development, thus preventing the growth of cancer cells and leading to their death by apoptosis. (keralapharmacist.com)

One such inhibitor is imatinib mesylate, which occupies the tyrosine kinase domain and inhibits BCR-ABL's influence on the cell cycle. (wikipedia.org)
Second generation BCR-ABL tyrosine-kinase inhibitors are also under development to inhibit BCR-ABL mutants resistant to imatinib. (wikipedia.org)
BCR-Abl is the target of selective inhibitors, such as imatinib (Gleevec), used in the treatment of CML. (umbc.edu)
The development of targeted therapies has also been followed by resistance, reminiscent of an evolutionary arms race, as exemplified by imatinib and other BCR-ABL inhibitors for the treatment of chronic myelogenous leukaemia. (nature.com)
Imatinib, marketed by Novartis as Gleevec (U.S.) or Glivec (Europe/Australia/Latin America), and sometimes referred to by its investigational name STI-571, is a tyrosine-kinase inhibitor used in the treatment of multiple cancers, most notably Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML). (keralapharmacist.com)
Because the BCR-Abl tyrosine kinase enzyme exists only in cancer cells and not in healthy cells, imatinib works as a form of targeted therapy-only cancer cells are killed through the drug's action. (keralapharmacist.com)
Imatinib is used to treat chronic myelogenous leukemia (CML), gastrointestinal stromal tumors (GISTs) and a number of other malignancies. (keralapharmacist.com)
One study demonstrated that imatinib mesylate was effective in patients with systemic mastocytosis, including those who had the D816V mutation in c-Kit.However, since imatinib binds to tyrosine kinases when they are in the inactive configuration and the D816V mutant of c-Kit is constitutively active, imatinib does not inhibit the kinase activity of the D816V mutant of c-Kit. (keralapharmacist.com)
As this is now a constitutively active tyrosine kinase, imatinib is used to decrease bcr-abl activity. (keralapharmacist.com)
Imatinib is quite selective for bcr-abl - it does also inhibit other targets mentioned above (c-kit and PDGF-R), but no other known tyrosine kinases. (keralapharmacist.com)
Interestingly, distinctly lower concentrations of bosutinib are required to ablate BCR-ABL phosphorylation when compared to the first-generation tyrosine kinase inhibitor imatinib (IM). (mdm2-receptor.com)

The BCR-ABL transcript encodes a tyrosine kinase, which activates mediators of the cell cycle regulation system, leading to a clonal myeloproliferative disorder. (wikipedia.org)
FLT3 ITD constitutively activates a signaling network, including the RAS- and STAT-signaling pathways. (biomedcentral.com)

Inhibition of the bcr-abl tyrosine kinase also stimulates its entry in to the nucleus, where it is unable to perform any of its normal anti-apoptopic functions. (keralapharmacist.com)
Binding mode and structural elements of Bcr-Abl inhibition are discussed with emphasis on pathways involved in this complex disease to determine alternative strategies and combination therapies. (eurekaselect.com)

This review outlines the Bcr-Abl dependent and independent mechanism of TKIs resistance development and the strategies used to overcome drug resistance, such as the development of ATP site and allosteric site inhibitors. (eurekaselect.com)

This gene is a partner in a fusion gene with the BCR gene in the Philadelphia chromosome, a characteristic abnormality in chronic myelogenous leukemia (CML) and rarely in some other leukemia forms. (wikipedia.org)
3 Myelofibrosis (MF) refers to the Philadelphia chromosome ( BCR-ABL1 )-negative myeloproliferative neoplasm (MPN) originating at the level of the multipotent hematopoietic stem cell. (haematologica.org)

This new fusion gene, BCR-ABL, encodes an unregulated, cytoplasm-targeted tyrosine kinase that allows the cells to proliferate without being regulated by cytokines. (wikipedia.org)

Abl is normally inactive and requires phosphorylation and myristoylation for activation. (umbc.edu)

Hematopoietic stem cell transplantation can be considered in young patients with chronic myelogenous leukemia in chronic phase if a human leukocyte antigen (HLA)-matched donor is available. (medscape.com)
In summary, we identify myostatin propeptide as a novel positive regulator of primitive CML cells and corresponding normal hematopoietic cells. (haematologica.org)
Our research focuses on developmental pathways that regulate hematopoietic cell growth and differentiation and are disrupted in the course of neoplastic transformation, particularly in leukemias and lymphomas. (stanford.edu)

In the cytoplasm, Abl plays a role in cell proliferation and survival. (umbc.edu)
From this perspective, the aim of this study was to analyze the expression and activation profile of STP involved in the mechanisms of cell proliferation/quiescence and survival of the progenitor CD34+ cells from chronic phase (CP) CML. (oncotarget.com)
Bosutinib is a potent inhibitor of CML cell proliferation in vitro and has demonstrated promising activity in CML patients resistant or intolerant to IM as well as in newly diagnosed patients with chronic phase CML (CML-CP). (mdm2-receptor.com)

Rowley, J.D. A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and giemsa staining. (eurekaselect.com)

The t(9;22) translocation results in the head-to-tail fusion of the BCR and ABL1 genes, leading to a fusion gene present in many cases of chronic myelogenous leukemia. (wikipedia.org)
The second provides for the highly sensitive detection of DSBs in the anaplastic lymphoma kinase (ALK) gene that result in a non-reciprocal (inversion) translocation (inv(2)(p21;p23)) associated with an ALK-positive non-small cell lung cancer (NSCLC). (ubc.ca)
The TEL gene is a frequent fusion partner of other tyr kinase oncogenes, including Tel/Abl, Tel/PDGFRbeta, and Tel/Jak2, found in patients with leukemia and myeloproliferative disorders. (umbc.edu)

Bosutinib (SKI-606), 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3- (4-methyl-1-piperazinyl) propoxy]-3-quinolinecarbonitrile monohydrate, is a competitive inhibitor of both Src and ABL tyrosine kinases. (mdm2-receptor.com)
Bosutinib is a potent dual inhibitor of the Src and ABL tyrosine kinases (Puttini et al. (mdm2-receptor.com)

The constitutively active Bcr-Abl tyrosine kinase plays a crucial role in chronic myelogenous leukemia (CML) pathogenesis. (tmu.edu.tw)
In addition to these basic issues concerning leukemia pathogenesis, we are devising new diagnostic procedures for detecting and monitoring leukemia patients based on molecular genetic abnormalities in the malignant cells. (stanford.edu)

We generated a triple transgenic mouse model, in which tamoxifen-inducible Cre-recombinase targets expression of a constitutively nuclear transcription factor NFATC1 to FLT3 ITD positive HSC. (biomedcentral.com)

Myeloproliferative diseases are a heterogenous group of disorders characterized by cellular proliferation of 1 or more hematologic cell lines in the peripheral blood, distinct from acute leukemia. (medscape.com)
Myeloproliferative diseases are a heterogeneous group of disorders characterized by cellular proliferation of one or more hematologic cell lines in the peripheral blood, distinct from acute leukemia. (medscape.com)

Aberrant NFAT signaling is causally involved in the development of chronic lymphocytic leukemia, non-Hodgkin lymphoma, pancreatic cancer, and several other malignancies. (biomedcentral.com)
Methotrexate, a folic acid analog/antimetabolite, can be curative for women with choriocarcinoma and is also useful for non-Hodgkin lymphomas and acute lymphocytic leukemias (ALLs) in children. (medquizzes.net)

Abl (or c-Abl) is a ubiquitously-expressed cytoplasmic (or nonreceptor) tyr kinase that contains SH3, SH2, and tyr kinase domains in its N-terminal region, as well as nuclear localization motifs, a putative DNA-binding domain, and F- and G-actin binding domains in its C-terminal tail. (umbc.edu)

They are also at risk of developing secondary acute leukemia from their underlying disorder, as well as from their treatment. (medscape.com)

In the pediatric population, B-acute lymphoblastic leukemia (B-ALL) is the most prevalent childhood hematological malignancy, as well as the leading cause of childhood cancer-related mortality. (biomedcentral.com)

Around the same time, and building on the observation that the vitamin folic acid could stimulate acute lymphoblastic leukemia (ALL) cells, Farber used folate analogs such as aminopterin and then amethopterin (methotrexate) to treat ALL, in what is often heralded as the first 'rational' drug development approach [ 4 ]. (biomedcentral.com)

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