Abl tyrosine kinase. Medical search. Frequent questions

Bcr-Abl tyrosine-kinase inhibitors (TKI) are the first-line therapy for most patients with chronic myelogenous leukemia (CML). (wikipedia.org)
Although next generation Abelson kinase inhibitors such as dasatinib or nilotinib may expand the role for these agents in MPDs, targeted inhibition of the mutant kinase JAK2 V617F is more likely to make significant therapeutic gains in the classic MPDs of PV, ET, and PMF. (elsevierpure.com)
Background BCR-ABL tyrosine kinase inhibitors (TKIs) are successful treatments extensively used to treat chronic myeloid leukemia (CML). (unamur.be)
Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP), previously treated with two or more tyrosine kinase inhibitors (TKIs). (nih.gov)
1997). The introduction of tyrosine kinase inhibitors (TKIs) in 2001 heralded the start of targeted therapies in hematopoietic cancers because of their distinct impact on tyrosine kinase, encoded by the CML-pathognomonic BCR-ABL gene (Kris et al. (ons.org)
You may first be treated in the chronic phase with drugs called tyrosine kinase inhibitors (TKIs). (webmd.com)
It is clear that tyrosine kinase inhibitors do not simply inhibit the enzyme, but rather remodel the machine," Superti-Furga aid. (sciencedaily.com)
Inhibitors of Bcr-abl. (tocris.com)
In light of the recent emergence of new therapeutics for rheumatoid arthritis, such as kinase inhibitors and biosimilars, a new nomenclature for disease-modifying antirheumatic drugs (DMARDs), which are currently often classified as synthetic (or chemical) DMARDs (sDMARDS) and biological DMARDs (bDMARDs), may be needed. (bmj.com)
Tyrosine kinase inhibitors (TKIs), a type of targeted therapy, are used in the treatment of CML. (cancercare.org)
This research relates to the use of BCR-ABL tyrosine kinase inhibitors for chronic myeloid leukemia (CML) and Ph+ acute lymphoblastic leukemia (ALL), as little is known about the long-term and late effects of these therapies in young people. (stanford.edu)
Before the advent of tyrosine kinase inhibitors (TKIs), the outcome of Ph+ ALL patients not eligible for allogeneic stem cell transplant (allo-SCT) was characterized by an extremely poor prognosis, a weak response to most chemotherapy combinations, short remission durations, and poor survival rates. (hindawi.com)
Bcr-Abl tyrosine-kinase inhibitors (TKI) do not definitively cure all CML patients. (bvsalud.org)
Treatment is with tyrosine kinase inhibitors (TKI) such as imatinib, dasatinib, nilotinib, bosutinib, and ponatinib, which significantly improve response and prolong survival. (msdmanuals.com)
Well, the best thing that happened to us is the invention of tyrosine kinase inhibitors (TKIs). (medscape.com)
Tyrosine kinase inhibitors (TKIs) are the drugs of choice for initial therapy of CML. (medscape.com)
Correction: HLA Polymorphisms Are Associated With Treatment-Free Remission Following Discontinuation of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia. (cdc.gov)

Even though the first Bcr-Abl TK inhibitor was named "the magic bullet" to cure cancer by Time magazine, a second generation of Bcr-Abl TKI was subsequently developed to combat the initial resistance that emerged. (wikipedia.org)
Imatinib (Gleevec) was discovered in 1992 and is regarded as first generation drug since it is the first Bcr-Abl tyrosine kinase inhibitor to be used in the treatment of CML. (wikipedia.org)
With a replacement of the imidazole group with a benzamido group, the compound's specificity increased while its activity as a kinase inhibitor remained the same. (wikipedia.org)
A Phase III Randomized Trial of Steroids + Tyrosine Kinase Inhibitor Induction with Chemotherapy or Blinatumomab for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia in Adults. (kucancercenter.org)
Methods: We evaluated the IRF4 expression kinetics during tyrosine kinase inhibitor (TKI) treatment in a cohort of 116 chronic myeloid leukemia (CML) patients to elucidate its role in the disease course. (karger.com)
Objectives Among Chronic Myeloid Leukemia (CML) patients treated with Tyrosine Kinase Inhibitor (TKI-imatinib-nilotinib), some showed a suboptimal response. (degruyter.com)
Moreover, in the 1-methyl-4-phenyl-1,2,4,6-tetrahydropyridine (MPTP) mouse model, dopamine deficiency caused increased phosphorylation of both Tyr15-Cdk5 and Thr75-DARPP-32 in the striatum, which could be attenuated by administration of L-3,4-dihydroxyphenylalanine and imatinib (STI-571), a selective c-Abl inhibitor. (frontiersin.org)
Glutamate inputs activate Cdk5, which inhibits postsynaptic dopamine D1 receptor (D1R)-mediated signaling by phosphorylating DARPP-32 at Thr75 (Thr75-DARPP-32) in the striatum, since DARPP-32 with Thr75 phosphorylation (DARPP-32-pThr75) functions as an inhibitor of cAMP-dependent protein kinase A (PKA). (frontiersin.org)
The introduction of imatinib, a selective inhibitor of the ABL tyrosine kinase, has revolutionized the treatment and the outcome of this subset of patients [ 1 ]. (hindawi.com)
Due to the introduction of imatinib, a tyrosine kinase inhibitor (TKI), CML patients now benefit from treatment ( 2 ). (spandidos-publications.com)
Imatinib mesylate (IM), a potent inhibitor of the BCR/ABL tyrosine kinase, has become standard first-line therapy for patients with chronic myeloid leukemia (CML), but the frequency of resistance increases in advancing stages of disease. (lu.se)
Critically, the combination of a tyrosine kinase inhibitor (TKI), i.e. (lu.se)
Distribution and frequency of tyrosine kinase inhibitor-associated long-term complications in children with chronic myeloid leukemia. (cdc.gov)
The new generation tyrosine kinase inhibitor improves the survival of chronic myeloid leukemia patients after allogeneic stem cell transplantation. (cdc.gov)

Until now, the impact of BCR-ABL TKIs on monocytes and macrophages have been little studied (Table 1).Aims The aim of this research is to determine using in vitro model, the effect of BCR-ABL TKIs on MMP production.Methods The 5 BCR-ABL TKIs were tested at 3 clinically relevant concentrations. (unamur.be)
Gels were finally colored by Coomassie blue to reveal lytic bands.Results The 5 BCR-ABL TKIs possess few impact on THP-1 viability. (unamur.be)
Other BCR-ABL TKIs do not affect the production and activity of MMP-2 and MMP-9 by THP-1.Conclusions New generation BCR-ABL TKIs have a few impact on macrophage survival as well as on MMP production and activity. (unamur.be)
These results do not suggest high impact of BCR-ABL TKIs on macrophages and vascular occlusive events are probably not mediated by impact on macrophages.Disclosures No relevant conflicts of interest to declare. (unamur.be)
Taken as a pill once or twice daily, TKIs target the protein made by the mutated BCR-ABL fusion gene. (cancercare.org)
Ponatinib is often used to treat CML that has a specific additional alteration in the BCR-ABL gene known as T315I, which makes CML cells resistant to treatment with other TKIs. (cancercare.org)

Drug discovery that specifically targeted the ATP binding site of a single kinase was regarded as quite a challenging task since hundreds of protein kinases were known in the human genome. (wikipedia.org)

In the presence of TKI the binding of ATP is blocked, phosphorylation is prevented and Bcr-Abl expressing cells either have a selective growth disadvantage or undergo apoptotic cell death. (wikipedia.org)
Upon cytokine stimulation, STAT5 tyrosine phosphorylation (pYSTAT5) is transient, while in diverse neoplastic cells persistent overexpression and enhanced pYSTAT5 are frequently found. (nature.com)
We found that O-GlcNAcylation and tyrosine phosphorylation act together to trigger pYSTAT5 levels and oncogenic transcription in neoplastic cells. (nature.com)
The expression of a mutated hyperactive gain-of-function (GOF) STAT5 without O-GlcNAcylation resulted in decreased tyrosine phosphorylation, oligomerization and transactivation potential and complete loss of oncogenic transformation capacity. (nature.com)
Our data show that O-GlcNAcylation of STAT5 is an important process that contributes to oncogenic transcription through enhanced STAT5 tyrosine phosphorylation and oligomerization driving myeloid transformation. (nature.com)
Cytokine binding to the cell surface leads to phosphorylation of the receptor complex by receptor associated Janus kinases (JAKs) at tyrosine residues. (nature.com)
7 The JAKs also trigger the activation and tyrosine phosphorylation of STAT5, causing parallel dimerization, nuclear translocation and tetramerization of STAT5. (nature.com)
One of the regulatory mechanisms that modulate the Cdk5 kinase activity is phosphorylation of conserved residues ( Dhavan and Tsai, 2001 ). (frontiersin.org)
These proteins are latent in the cytoplasm and become activated through tyrosine phosphorylation which typically occurs through cytokine receptor associated kinases (JAKs) or growth factor receptor tyrosine kinases. (nih.gov)
Recently a number of non-receptor tyrosine kinases (for example src and abl) have been found to cause STAT phosphorylation. (nih.gov)
The results revealed that AVM inhibited the phosphorylation of BCR/ABL and their subsequent molecular signals including AKT and MAPK activation. (spandidos-publications.com)

This abnormality was discovered by Peter Nowell in 1960 and is a consequence of fusion between the Abelson (Abl) tyrosine kinase gene at chromosome 9 and the break point cluster (Bcr) gene at chromosome 22, resulting in a chimeric oncogene (Bcr-Abl) and a constitutively active Bcr-Abl tyrosine kinase that has been implicated in the pathogenesis of CML. (wikipedia.org)
c-Abelson tyrosine kinase (c-Abl) is known to phosphorylate Cdk5 at Tyr15 (Tyr15-Cdk5) and thereby facilitates the Cdk5 activity. (frontiersin.org)

Bcr-Abl was regarded as highly attractive target for drug intervention since the Bcr-Abl fusion gene encodes a constitutively activated kinase. (wikipedia.org)
The Abl-related gene (Arg) requires its F-actin-microtubule cross-linking activity to regulate lamellipodial dynamics during fibroblast adhesion. (nih.gov)
pronounced "sarc", as it is short for sarcoma), is a non-receptor tyrosine kinase protein that in humans is encoded by the SRC gene. (wikipedia.org)
It belongs to a family of Src family kinases and is similar to the v-Src (viral Src) gene of Rous sarcoma virus. (wikipedia.org)
It carries a new gene called bcr-abl, which sets off a process that creates abnormal white blood cells. (webmd.com)
They kill off CML blood cells by blocking the protein made by the abnormal gene bcr-abl. (webmd.com)
CML is triggered by a chromosomal abnormality (an error during cell growth) in which the ABL gene is mistakenly joined to the BCR gene, forming a mutated BCR-ABL "fusion gene. (cancercare.org)
The BCR-ABL gene leads to the production of an abnormal protein that fuels the growth of leukemia cells. (cancercare.org)
q11) resulting in a chimeric bcr-abl (e1a2 breakpoint) fusion gene that encodes a 190 KD protein (p190) with constitutively active tyrosine kinase activity that can alter multiple signaling pathways, contributing to tumor growth and proliferation. (hindawi.com)
The ATM gene encodes a large protein that belongs to a family of kinases possessing a highly conserved C-terminal kinase domain related to the phosphatidylinositol 3-kinase domain. (bmj.com)
An abnormal chromosomal translocation known as t(9;22) results in the establishment of the Philadelphia chromosome, which contains the BCR-ABL gene, culminating in the development of this syndrome ( 1 ). (spandidos-publications.com)
During this translocation, a piece of chromosome 9 containing the oncogene ABL is translocated to chromosome 22 and fused to the BCR gene. (msdmanuals.com)
The chimeric fusion gene BCR-ABL is responsible for production of the oncoprotein bcr-abl tyrosine kinase. (msdmanuals.com)

Orthologous to human ABL2 (ABL proto-oncogene 2, non-receptor tyrosine kinase). (nih.gov)

inhibits proliferation and induces apoptosis in Bcr-Abl-expressing cells. (tocris.com)
Glutamate inputs activate cyclin-dependent kinase 5 (Cdk5), which inhibits postsynaptic dopamine signaling by phosphorylating DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, 32 kDa) at Thr75 in the striatum. (frontiersin.org)
It is thus concluded that AVM inhibits the activity of BCR/ABL and their subsequent molecular signals, including AKT and MAPK, resulting in cytotoxicity via apoptosis. (spandidos-publications.com)

C-Abl (Abl) regulates multiple cellular processes, including proliferation, survival, shape determination and motility, and participates in cellular responses to genotoxic and oxidative stress stimuli. (huji.ac.il)

and transmembrane receptor protein tyrosine kinase signaling pathway. (nih.gov)
A Role for the Non-Receptor Tyrosine Kinase Abl2/Arg in Experimental Neuroinflammation. (nih.gov)
c-Src can be activated by many transmembrane proteins that include: adhesion receptors, receptor tyrosine kinases, G-protein coupled receptors and cytokine receptors. (wikipedia.org)
Most studies have looked at the receptor tyrosine kinases and examples of these are platelet derived growth factor receptor (PDGFR) pathway and epidermal growth factor receptor (EGFR). (wikipedia.org)
DDR1, also known as CAK, CD167a, RTK6, and TrkE, is a 120-140 kDa type I transmembrane glycoprotein that belongs to the discoidin-like domain containing subfamily of receptor tyrosine kinases and serve as receptors for collagen. (rndsystems.com)
Tau interacts with src-family non-receptor tyrosine kinases. (eu.org)
Non-receptor tyrosine kinases encoded by the C-ABL GENES. (bvsalud.org)

The MPDs (which include polycythemia vera (PV), essential thrombocythemia (ET), chronic eosinophilic leukemia (CEL), primary myelofibrosis (PMF), chronic myelomono- cytic leukemia (CMML), and systemic mast cell disease (SMCD)) exclude chronic myeloid leukemia (CML) because of the pathognomic importance of the BCR-ABL translocation for the diagnosis and treatment of this disorder with imatinib mesylate. (elsevierpure.com)
We have shown here that IM induces autophagy in CML blast crisis cell lines, CML primary cells, and p210BCR/ABL-expressing myeloid precursor cells. (lu.se)
c-Abl plays a role in normal HEMATOPOIESIS especially of the myeloid lineage. (bvsalud.org)
Differences in Variants in the Structural Domain of BCR-ABL1 Kinase between Chinese Han and Minority Patients with Chronic Myeloid Leukemia by Sanger Sequencing and Next-Generation Sequencing. (cdc.gov)

Selective for Bcr-Abl over a panel of serine, threonine and tyrosine kinases. (tocris.com)

Association of p62, a multifunctional SH2- and SH3-domain-binding protein, with src family tyrosine kinases, Grb2, and phospholipase C gamma-1. (eu.org)

Chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm that expresses the Philadelphia chromosome and constitutively activated Bcr-Abl tyrosine kinase in hematopoietic progenitor cells. (bvsalud.org)

This study aims to analyze the relationship between TKI Cmin∞ ${C}_{min}\hat{\infty }$ and BCL-ABL ratio in chronic-phase CML patients. (degruyter.com)

Ph+ acute lymphoblastic leukemia (Ph+ ALL) is a high-risk acute leukemia with poor prognosis, in which the specific t(9;22)(q34;q11) translocation results in a chimeric bcr-abl (e1a2 breakpoint) and in a 190 KD protein (p190) with constitutive tyrosine kinase activity. (hindawi.com)

Cyclin-dependent kinase 5 (Cdk5) is a member of the Cdk family of serine/threonine kinases and is abundantly expressed in the brain ( Dhavan and Tsai, 2001 ). (frontiersin.org)

c-Src phosphorylates specific tyrosine residues in other tyrosine kinases. (wikipedia.org)

8 , 9 The protein is a member of a novel family of large proteins, which show sequence homology to the catalytic domain of phosphatidylinositol 3 kinase, 3 and are implicated in cell cycle regulation, signal transduction, and the response to DNA damage. (bmj.com)
Identification of two SH3-binding motifs in the regulatory subunit of phosphatidylinositol 3-kinase. (eu.org)

Empiric use of imatinib mesylate against the spectrum of BCR-ABL negative MPDs has had mixed results. (elsevierpure.com)

Elimination of BCR/ABL-dependent intracellular signals triggers apoptosis, but it is unclear whether this activates additional cell survival and/or death pathways. (lu.se)
The bcr-abl oncoprotein has uncontrolled tyrosine kinase activity, which deregulates cellular proliferation, decreases adherence of leukemia cells to the bone marrow stroma, and protects leukemic cells from normal programmed cell death (apoptosis). (msdmanuals.com)

Deregulated activity of the Abl protein tyrosine kinase is oncogenic in humans and in animals. (torvergata.it)
Oncogenic forms of Abl efficiently enhanced the ability of Xenopus oocytes to enter M phase following stimulation by progesterone. (torvergata.it)
Oncogenic transformation of c-abl arises when specific N-terminal amino acids are deleted, releasing the kinase from negative regulation. (bvsalud.org)

Regulation of MT dynamics via direct binding of an Abl family kinase. (nih.gov)
To define the role of Abl in the regulation of adult T cells we ablated Abl exclusively in T cells by generating mice with floxed abl alleles and expressing an Lck-Cre transgene (Abl-T -/- ). These mice exhibited thymic atrophy and abnormally reduced T cell numbers in the periphery. (huji.ac.il)
c-Src should not be confused with CSK (C-terminal Src kinase), an enzyme that phosphorylates c-Src at its C-terminus and provides negative regulation of Src's enzymatic activity. (wikipedia.org)
Altogether, this suggests that an SH3 domain-dependent Abl regulation mechanism similar to the one observed in mammalian cells operates in Xenopus oocytes. (torvergata.it)
Regulation of Rad51 function by c-Abl in response to DNA damage. (eu.org)

Consequently, Abl-T -/- mice exhibited impaired ability to reject syngeneic tumor, to induce T-mediated tumor cell killing, and to generate anti-tumor antibodies. (huji.ac.il)

New forms of resistance can arise as: missense mutations within the Abl kinase domain, over-expression of Bcr-Abl, increased production of transmembrane plasma proteins, or the constitutive activation of downstream signaling molecules such as Src-family kinases. (wikipedia.org)
4 , 10 There is evidence to suggest that these proteins respond to DNA damage by phosphorylating one or more substrates, including p53, c-Abl, and replication protein A (RPA), to recruit proteins to regions of DNA repair and/or to activate radiation signal transduction pathways. (bmj.com)
In contrast, in many cancerous cell lines and tumors, where growth factor dysregulation is frequently at the heart of cellular transformation, the STAT proteins (in particular Stats 1, 3 and 5) are persistently tyrosine phosphorylated or activated. (nih.gov)

In the DASISION (DASatinib versus Imatinib Study In treatment-Naive CML patients) trial, final 5-year analysis showed significantly higher MMR and molecular response with ≥4.5 log reduction of BCR-ABL on the International Scale (MR4.5) in patients with newly diagnosed CP-CML who received dasatinib, 100 mg once daily (n = 259), than in those who received imatinib, 400 mg once daily (n = 260). (medscape.com)

Compounds have been developed to selectively inhibit the tyrosine kinase. (wikipedia.org)
Due to increasing resistance and intolerance to imatinib efforts were made to develop new drugs that could inhibit the Bcr-Abl tyrosine kinase. (wikipedia.org)

The activation of c-Src causes the dephosphorylation of the tyrosine 527. (wikipedia.org)
Abl-enhanced maturation was normal as judged by accumulation of Mos as well as activation of MAP kinase and Cdc2/CyclinB (MPF). (torvergata.it)
Concomitant with maturation and activation of these kinases, Abl became extensively phosphorylated. (torvergata.it)
Focusing on preventing BCR-ABL activation is quite efficient, as imatinib has demonstrated, but may not be the optimal option. (spandidos-publications.com)

Scar/WAVE-1, a Wiskott-Aldrich syndrome protein, assembles an actin-associated multi-kinase scaffold. (eu.org)

and protein tyrosine kinase activity. (nih.gov)
We have tested the activity of human c-Abl microinjected into oocytes of Xenopus laevis. (torvergata.it)
In contrast to versions of Abl capable of transforming mammalian cells, which were highly active when introduced into oocytes, the activity of wild type c-Abl was inhibited. (torvergata.it)
Maturation enhancement by microinjection into Xenopus oocytes represents a useful novel assay for analyzing Abl activity. (torvergata.it)
Phosphoproteomic techniques have been widely employed to identify kinase activity, which may lend itself to pharmaceutical blockade. (nature.com)
Our results suggest a functional link of Cdk5-pTyr15 with postsynaptic dopamine and glutamate signals through the c-Abl kinase activity in the striatum. (frontiersin.org)
IM-induced autophagy did not involve c-Abl or Bcl-2 activity but was associated with ER stress and was suppressed by depletion of intracellular Ca2+, suggesting it is mechanistically. (lu.se)

These results demonstrate a cell-autonomous role for Abl in T cell function and survival. (huji.ac.il)

As a result, cells expressing different forms of BCR/ABL were recruited for the present study, including K562 (human wild‑type) or TCCY‑T315I (human imatinib‑resistant) and the Ba/F3‑(T315I/E279K/Y253H) (mouse BCR/ABL point mutation‑transfected cells). (spandidos-publications.com)
Interestingly, AVM appeared to be more sensitive to imatinib‑resistant (T315I, Y253H, and E279K) than wild‑type BCR/ABL cells, indicating its potential to overcome imatinib‑resistant severe issues in CML. (spandidos-publications.com)
Thus, cells expressing different forms of BCR/ABL were recruited for the present study, including K562 [human wild-type (WT)] or TCCY-T315I [human imatinib-resistant (IR)] and the Ba/F3-(T315I/E279K/Y253H) (mouse BCR/ABL point mutation-tranfected cells). (spandidos-publications.com)

Due to bcr-abl fusion, the corresponding p190 joint region contains an amino acid sequence unique to the oncoprotein in addition to a novel amino acid, not belonging to either BCR or ABL sequences, created at the exact fusion point. (hindawi.com)
Alterations in the BCR-ABL sequences are one of the most common explanations ( 3 ). (spandidos-publications.com)

Imatinib-nilotinib Cmin∞${C}_{min}\hat{\infty }$ and BCR-ABL ratio were measured using HPLC and RT-qPCR. (degruyter.com)
Conclusions There were high interindividual variations of imatinib and nilotinib correlated with BCR-ABL ratio, but no correlation in nilotinib. (degruyter.com)

Recently "natural" bcr-abl breakpoint-specific cytotoxic T lymphocytes (CTLs) were found in the bone marrow of Ph+ ALL patients treated with imatinib correlating with a better response to this TKI [ 6 ]. (hindawi.com)

This induces long-range allostery via protein domain dynamics, causing the structure to be destabilized, resulting in the opening up of the SH3, SH2 and kinase domains and the autophosphorylation of the residue tyrosine 416. (wikipedia.org)

Superti-Furga's team has been investigating a particular enzyme, a tyrosine kinase called Bcr-Abl, which is involved in leukaemia. (sciencedaily.com)

Importantly, Abl deficient T cells displayed abnormally reduced response to mitogenic stimulation in vitro. (huji.ac.il)

Two additional kinase deficient splice forms are expressed in colon cancer. (rndsystems.com)

Within three months of TKI treatment, blood counts are expected to be clear of signs of the CML and "early molecular response" is the goal, with BCR-ABL levels falling to 1/10th of their original level. (cancercare.org)

Anatomy18

Organisms6

Diseases2

Chemicals and Drugs170

Analytical, Diagnostic and Therapeutic Techniques and Equipment13

Phenomena and Processes42

Disciplines and Occupations1

Information Science3

Inhibitors17

Inhibitor14

TKIs6

Protein kinases1

Phosphorylation11

Abelson2

Gene13

Oncogene1

Inhibits3

Regulates1

Receptor7

Myeloid4

Selective1

Family tyrosine1

Constitutively activated1

Chronic Phase1

Chimeric1

20011

Residues1

Phosphatidylinositol 3 kina2

Imatinib mesylate1

Apoptosis2

Oncogenic3

Regulation5

Tumor1

Proteins3

Dasatinib1

Inhibit2

Activation4

Actin1

Activity7

Survival1

T315I3

Sequences2

Nilotinib2

Patients1

Residue1

Leukaemia1

Stimulation1

Deficient1

Molecular1