abl genes


Summary: Retrovirus-associated DNA sequences (abl) originally isolated from the Abelson murine leukemia virus (Ab-MuLV). The proto-oncogene abl (c-abl) codes for a protein that is a member of the tyrosine kinase family. The human c-abl gene is located at 9q34.1 on the long arm of chromosome 9. It is activated by translocation to bcr on chromosome 22 in chronic myelogenous leukemia.

Top Publications

  1. Primo D, Flores J, Quijano S, Sanchez M, Sarasquete M, del Pino Montes J, et al. Impact of BCR/ABL gene expression on the proliferative rate of different subpopulations of haematopoietic cells in chronic myeloid leukaemia. Br J Haematol. 2006;135:43-51 pubmed
  2. Iacobucci I, Lonetti A, Messa F, Cilloni D, Arruga F, Ottaviani E, et al. Expression of spliced oncogenic Ikaros isoforms in Philadelphia-positive acute lymphoblastic leukemia patients treated with tyrosine kinase inhibitors: implications for a new mechanism of resistance. Blood. 2008;112:3847-55 pubmed publisher
    ..These results establish a previously unknown link between specific molecular defects that involve alternative splicing of the IKZF1 gene and the resistance to TKIs in Ph+ ALL patients...
  3. Srinivasan D, Sims J, Plattner R. Aggressive breast cancer cells are dependent on activated Abl kinases for proliferation, anchorage-independent growth and survival. Oncogene. 2008;27:1095-105 pubmed
    ..Since activation of Abl kinases affects multiple steps of breast cancer development and progression, Abl kinase inhibitors are likely to be effective agents for the treatment of breast cancers containing highly active Abl kinases. ..
  4. Wong S, Witte O. The BCR-ABL story: bench to bedside and back. Annu Rev Immunol. 2004;22:247-306 pubmed
    ..The successes and limitations of Imatinib mesylate hold general lessons for the development of alternative molecular targeted therapies in oncology. ..
  5. Pendergast A. The Abl family kinases: mechanisms of regulation and signaling. Adv Cancer Res. 2002;85:51-100 pubmed
  6. Manley P, Breitenstein W, Br├╝ggen J, Cowan Jacob S, Furet P, Mestan J, et al. Urea derivatives of STI571 as inhibitors of Bcr-Abl and PDGFR kinases. Bioorg Med Chem Lett. 2004;14:5793-7 pubmed
    ..It was also possible to differentiate between c-Abl and PDGFR kinase inhibition, with compound 22 being selective towards Abl and 23 selective for PDGFR. ..
  7. Hernandez S, Krishnaswami M, Miller A, Koleske A. How do Abl family kinases regulate cell shape and movement?. Trends Cell Biol. 2004;14:36-44 pubmed
    ..Emerging evidence suggests that Abl family kinases can use these domains to directly organize cytoskeletal structure in vivo. ..
  8. Sexl V, Piekorz R, Moriggl R, Rohrer J, Brown M, Bunting K, et al. Stat5a/b contribute to interleukin 7-induced B-cell precursor expansion, but abl- and bcr/abl-induced transformation are independent of stat5. Blood. 2000;96:2277-83 pubmed
    ..We demonstrate that the absence of Stat5a/b is not essential for the induction of lymphoid or myeloid tumors in vivo or on the ability to transform bone marrow cells in vitro. ..
  9. Gorre M, Mohammed M, Ellwood K, Hsu N, Paquette R, Rao P, et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science. 2001;293:876-80 pubmed
    ..These studies provide evidence that genetically complex cancers retain dependence on an initial oncogenic event and suggest a strategy for identifying inhibitors of STI-571 resistance. ..

More Information


  1. Soverini S, Martinelli G, Rosti G, Bassi S, Amabile M, Poerio A, et al. ABL mutations in late chronic phase chronic myeloid leukemia patients with up-front cytogenetic resistance to imatinib are associated with a greater likelihood of progression to blast crisis and shorter survival: a study by the GIMEMA Working Party o. J Clin Oncol. 2005;23:4100-9 pubmed
  2. Martinelli G, Soverini S, Rosti G, Baccarani M. Dual tyrosine kinase inhibitors in chronic myeloid leukemia. Leukemia. 2005;19:1872-9 pubmed
    ..Here, we review the development, the mode of action and the preclinical or early clinical evaluation of several novel dual Src and Abl kinase inhibitors. ..
  3. Roche Lestienne C, Soenen Cornu V, Grardel Duflos N, Lai J, Philippe N, Facon T, et al. Several types of mutations of the Abl gene can be found in chronic myeloid leukemia patients resistant to STI571, and they can pre-exist to the onset of treatment. Blood. 2002;100:1014-8 pubmed
  4. Goldman J, Melo J. Chronic myeloid leukemia--advances in biology and new approaches to treatment. N Engl J Med. 2003;349:1451-64 pubmed
  5. Barnes D, Schultheis B, Adedeji S, Melo J. Dose-dependent effects of Bcr-Abl in cell line models of different stages of chronic myeloid leukemia. Oncogene. 2005;24:6432-40 pubmed
    ..These findings suggest that the level of Bcr-Abl may be essential in determining the phenotype of the leukemic clone at different stages of the disease. ..
  6. Sattler M, Pride Y, Quinnan L, Verma S, Malouf N, Husson H, et al. Differential expression and signaling of CBL and CBL-B in BCR/ABL transformed cells. Oncogene. 2002;21:1423-33 pubmed
    ..These results demonstrate that BCR/ABL signals differentially through CBL and CBL-B, with downregulation of the CBL-B protein potentially contributing to BCR/ABL-mediated transformation. ..
  7. Hoelbl A, Kovacic B, Kerenyi M, Simma O, Warsch W, Cui Y, et al. Clarifying the role of Stat5 in lymphoid development and Abelson-induced transformation. Blood. 2006;107:4898-906 pubmed
    ..These findings show distinct lymphoid defects for Stat5a/b(DeltaN/DeltaN) and Stat5a/b(null/null) mice and define a novel functional role for the N-termini of Stat5a/b in B-lymphoid transformation. ..
  8. Sharma S, Gajowniczek P, Way I, Lee D, Jiang J, Yuza Y, et al. A common signaling cascade may underlie "addiction" to the Src, BCR-ABL, and EGF receptor oncogenes. Cancer Cell. 2006;10:425-35 pubmed
    ..Moreover, these observations implicate a common profile of signal attenuation for multiple oncogenes and suggest that "addiction" associated with apoptosis reflects an active rather than a passive process. ..
  9. Kain K, Klemke R. Inhibition of cell migration by Abl family tyrosine kinases through uncoupling of Crk-CAS complexes. J Biol Chem. 2001;276:16185-92 pubmed
    ..Thus, Abl and Arg kinases play a critical role in preventing cell migration through regulation of Crk and CAS adaptor protein complexes, which are necessary for cell movement. ..
  10. Peters D, Hoover R, Gerlach M, Koh E, Zhang H, Choe K, et al. Activity of the farnesyl protein transferase inhibitor SCH66336 against BCR/ABL-induced murine leukemia and primary cells from patients with chronic myeloid leukemia. Blood. 2001;97:1404-12 pubmed
    ..As an oral, nontoxic compound with a mechanism of action distinct from that of ABL tyrosine kinase inhibition, FTI SCH66336 shows promise for the treatment of BCR/ABL-induced leukemia. ..
  11. Morinaga K, Yamauchi T, Kimura S, Maekawa T, Ueda T. Overcoming imatinib resistance using Src inhibitor CGP76030, Abl inhibitor nilotinib and Abl/Lyn inhibitor INNO-406 in newly established K562 variants with BCR-ABL gene amplification. Int J Cancer. 2008;122:2621-7 pubmed publisher
    ..Because BCR-ABL gene amplification occurs in blast crisis, these inhibitors might overcome IM resistance in such patients' leukemia. ..
  12. Comer A, Ahern Djamali S, Juang J, Jackson P, Hoffmann F. Phosphorylation of Enabled by the Drosophila Abelson tyrosine kinase regulates the in vivo function and protein-protein interactions of Enabled. Mol Cell Biol. 1998;18:152-60 pubmed
    ..Phosphorylation of Ena by Abl inhibited the binding of Ena to SH3 domains in vitro, suggesting that one effect of Ena phosphorylation may be to modulate its association with other proteins. ..
  13. Henkemeyer M, West S, Gertler F, Hoffmann F. A novel tyrosine kinase-independent function of Drosophila abl correlates with proper subcellular localization. Cell. 1990;63:949-60 pubmed
  14. Pear W, Miller J, Xu L, Pui J, Soffer B, Quackenbush R, et al. Efficient and rapid induction of a chronic myelogenous leukemia-like myeloproliferative disease in mice receiving P210 bcr/abl-transduced bone marrow. Blood. 1998;92:3780-92 pubmed
    ..These results demonstrate that murine CML recapitulates important features of human CML. As such, it should be an excellent model for addressing specific issues relating to the pathogenesis and treatment of this disease. ..
  15. Jelinek F, Sobotkova E, Vonka V. Characteristics of two mouse bcr-abl-transformed cell lines. II. Pathological lesions induced in mice. Folia Biol (Praha). 2005;51:93-102 pubmed
    ..We classified the disease induced by both of the cell lines as acute myeloid undifferentiated leukaemia (AML MO). ..
  16. Wong S, McLaughlin J, Cheng D, Shannon K, Robb L, Witte O. IL-3 receptor signaling is dispensable for BCR-ABL-induced myeloproliferative disease. Proc Natl Acad Sci U S A. 2003;100:11630-5 pubmed
    ..However, the IL-3Rbetac/beta chain could act as a cofactor in BCR-ABL-induced leukemogenesis by activation of its many known oncogenic signaling pathways. ..
  17. Isoda T, Ford A, Tomizawa D, van Delft F, De Castro D, Mitsuiki N, et al. Immunologically silent cancer clone transmission from mother to offspring. Proc Natl Acad Sci U S A. 2009;106:17882-5 pubmed publisher
    ..e., foreign to the infant), suggesting a possible mechanism for immune evasion. ..
  18. Gozzetti A, Bocchia M, Calabrese S, Pirrotta M, Crupi R, Raspadori D, et al. Promyelocytic blast crisis of chronic myelogenous leukemia during imatinib treatment. Acta Haematol. 2007;117:236-7 pubmed
  19. Nomdedeu J, Perea G, Estivill C, Badell I, Lasa A, Aventin A. Microsatellite instability may involve the pentanucleotide repeat of the PIG3 promoter in bcr/abl acute lymphoblastic leukemia. Leuk Res. 2008;32:186-8 pubmed
  20. Ikegame K, Mukouchi C, Kunitomi A, Konaka Y, Kawakami M, Nishida S, et al. Successful treatment of bcr/abl-positive acute mixed lineage leukemia by unmanipulated bone marrow transplantation from an HLA-haploidentical (3-antigen-mismatched) cousin. Bone Marrow Transplant. 2003;31:1165-8 pubmed
    ..This successful case suggests that HLA-haploidentical transplantation using unmanipulated marrow from a distantly related relative can be considered for patients in urgent situations who do not have HLA-identical donors. ..
  21. el Awady M, Abdalla N, Salem A, Samir S, Nour A. Differential display analysis of mRNAs in chronic myelogenous leukaemia. East Mediterr Health J. 2001;7:707-15 pubmed
    ..Our results support the use of differential display not only for characterization of the CML differentially expressed genes but also to locate patterns that can be implemented as valuable fingerprints for each phase of CML. ..
  22. de Groot R, Raaijmakers J, Lammers J, Koenderman L. STAT5-Dependent CyclinD1 and Bcl-xL expression in Bcr-Abl-transformed cells. Mol Cell Biol Res Commun. 2000;3:299-305 pubmed
    ..These results suggest that STAT5 contributes to transformation by Bcr-Abl by induction of cyclin D1 and bcl-xL expression. ..
  23. Simpson L, He X, Pins M, Huang X, Campbell S, Yang X, et al. Renal medullary carcinoma and ABL gene amplification. J Urol. 2005;173:1883-8 pubmed
    ..We characterized the clinical course of renal medullary carcinoma (RMC) and performed an expanded analysis of BCR-ABL...
  24. La Starza R, Trubia M, Testoni N, Ottaviani E, Belloni E, Crescenzi B, et al. Clonal eosinophils are a morphologic hallmark of ETV6/ABL1 positive acute myeloid leukemia. Haematologica. 2002;87:789-94 pubmed
  25. Sorel N, Roy L, Martineau G, Guilhot F, Turhan A, Chomel J. Sequential emergence of ABL-kinase mutations with loss of unmutated BCR-ABL allele during targeted therapies of CML. Blood. 2006;108:1782-3 pubmed
  26. Manetti F, Pucci A, Magnani M, Locatelli G, Brullo C, Naldini A, et al. Inhibition of Bcr-Abl phosphorylation and induction of apoptosis by pyrazolo[3,4-d]pyrimidines in human leukemia cells. ChemMedChem. 2007;2:343-53 pubmed
    ..Finally, molecular modeling simulations were also performed to hypothesize the binding mode of the compounds into the Abl binding site. ..
  27. Fugazza G, Garuti A, Marchelli S, Miglino M, Bruzzone R, Gatti A, et al. Masked Philadelphia chromosome due to atypical BCR/ABL localization on the 9q34 band and duplication of the der(9) in a case of chronic myelogenous leukemia. Cancer Genet Cytogenet. 2005;163:173-5 pubmed
  28. Nakagawa Y, Furusyo N, Taniai H, Henzan H, Tsuchihashi T, Hayashi J. Chronic myelogenous leukemia that occurred two years after the diagnosis of adult Still's disease. Intern Med. 2005;44:994-7 pubmed
    ..No case of CML was reported to develop from ASD. Because a diagnosis of ASD is based on the exclusion of other diseases, we must be cognizant of the possibility of the development of concurrent diseases. ..
  29. Hochhaus A, Lahaye T, Kreil S, Berger U, Metzgeroth G, Hehlmann R. [Selective inhibition of tyrosine kinases - a new therapeutic principle in oncology]. Onkologie. 2001;24 Suppl 5:65-71 pubmed
    ..Clinical responses to STI571 in various malignancies may stimulate greater interest in the clinical use of tyrosine kinase inhibitors. ..
  30. Ongkeko W, An Y, Chu T, Aguilera J, Dang C, Wang Rodriguez J. Gleevec suppresses p63 expression in head and neck squamous cell carcinoma despite p63 activation by DNA-damaging agents. Laryngoscope. 2006;116:1390-6 pubmed
    ..Further development of antibodies that can discriminate between TAp63 and DeltaNp63 will be needed to determine the specific effects of Gleevec on p63 in HNSCC. ..
  31. Onida F, Ball G, Kantarjian H, Smith T, Glassman A, Albitar M, et al. Characteristics and outcome of patients with Philadelphia chromosome negative, bcr/abl negative chronic myelogenous leukemia. Cancer. 2002;95:1673-84 pubmed
    ..Bcr/abl negative CML is a distinct clinical entity associated with very poor prognosis. Two risk categories are identifiable using a simple scoring system based on age, hemoglobin level, and leukocyte number. ..
  32. Lassila M, Allen T, Cao Z, Thallas V, Jandeleit Dahm K, Candido R, et al. Imatinib attenuates diabetes-associated atherosclerosis. Arterioscler Thromb Vasc Biol. 2004;24:935-42 pubmed
    ..Tyrosine kinase inhibition with imatinib appears to be a novel therapeutic option to retard the development of atherosclerosis, specifically in the context of diabetes. ..
  33. Ding K, Su Y, Pang L, Lu Q, Wang Z, Zhang S, et al. Inhibition of apoptosis by downregulation of hBex1, a novel mechanism, contributes to the chemoresistance of Bcr/Abl+ leukemic cells. Carcinogenesis. 2009;30:35-42 pubmed publisher
    ..These data provide evidence that expression of hBex1 in leukemic cells is a novel mechanism by which chemoresistance is achieved and suggests that hBex1 is a potential molecular target for the development of novel leukemia treatments. ..
  34. Wei Y, Liang Y, Xu L, Zhao X. The antiproliferation effect of berbamine on k562 resistant cells by inhibiting NF-kappaB pathway. Anat Rec (Hoboken). 2009;292:945-50 pubmed publisher
    ..The mechanisms may be related at least in part, to inhibit BCR-ABL and its downstream NF-kappaB signaling. Berbamine may provide an alternative candidate for the treatment of patients with CML resistant to imatinib therapy. ..
  35. Teckchandani A, Feshchenko E, Tsygankov A. c-Cbl facilitates fibronectin matrix production by v-Abl-transformed NIH3T3 cells via activation of small GTPases. Oncogene. 2001;20:1739-55 pubmed
    ..The results of this study also demonstrate that ubiquitination is essential for the observed effects of c-Cbl on fibronectin matrix production and cell adhesion. ..
  36. Fan Q, Weiss W. Chemical genetic approaches to the development of cancer therapeutics. Curr Opin Genet Dev. 2006;16:85-91 pubmed
    ..Elucidation of the mechanisms through which specific small molecule drug-like agents impact crucial cancer pathways should yield important and clinically translatable insights into the use of similar agents in patients. ..
  37. Zhu H, Liu Y, Qin Y, Li J, Chang Y, Wang Y, et al. [Detection of PML/RARalpha gene transcripts in 46 newly diagnosed acute promyelocytic leukemia patients by real-time quantitative reverse-transcription polymerase chain reaction]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2007;15:1-5 pubmed
    ..There was no significant difference about PML/RARalpha mRNA expression of both bcr3-form and bcr1-form APL patients. Type of PML/RARalpha transcripts is related with the morphology and immunophenotype. ..
  38. Li X, Yang J, Chen X, Liu J, Li H, Zheng J, et al. A report of early cytogenetic response to imatinib in two patients with chronic myeloid leukemia at accelerated phase and carrying the e19a2 BCR-ABL transcript. Cancer Genet Cytogenet. 2007;176:166-8 pubmed
    ..Moreover, these patients showed early response to imatinib treatment. Our study highlights the clinical potential of imatinib for this patient subgroup. ..
  39. Sullivan C, Peng C, Chen Y, Li D, Li S. Targeted therapy of chronic myeloid leukemia. Biochem Pharmacol. 2010;80:584-91 pubmed publisher
    ..In this review, we will discuss current targeted therapies of CML using BCR-ABL kinase inhibitors, with a focus on the importance of developing a targeted therapy of CML through identification of target genes in CML LSCs. ..
  40. Cebo C, Da Rocha S, Wittnebel S, Turhan A, Abdelali J, Caillat Zucman S, et al. The decreased susceptibility of Bcr/Abl targets to NK cell-mediated lysis in response to imatinib mesylate involves modulation of NKG2D ligands, GM1 expression, and synapse formation. J Immunol. 2006;176:864-72 pubmed
  41. Corm S, Biggio V, Roche Lestienne C, Lai J, Yakoub Agha I, Philippe N, et al. Coexistence of AML1/RUNX1 and BCR-ABL point mutations in an imatinib-resistant form of CML. Leukemia. 2005;19:1991-2 pubmed
  42. Gustafson W, Ray S, Jamieson L, Thompson E, Brasier A, Fields A. Bcr-Abl regulates protein kinase Ciota (PKCiota) transcription via an Elk1 site in the PKCiota promoter. J Biol Chem. 2004;279:9400-8 pubmed
    ..Our results indicate that Bcr-Abl-mediated transformation involves transcriptional activation of the PKCiota gene, which in turn is required for Bcr-Abl-mediated chemoresistance. ..
  43. Shteper P, Siegfried Z, Asimakopoulos F, Palumbo G, Rachmilewitz E, Ben Neriah Y, et al. ABL1 methylation in Ph-positive ALL is exclusively associated with the P210 form of BCR-ABL. Leukemia. 2001;15:575-82 pubmed
    ..We put forth a model that correlates the different types of leukemias with the different levels of ABL1 promoter methylation. ..
  44. Advani A, Pendergast A. Bcr-Abl variants: biological and clinical aspects. Leuk Res. 2002;26:713-20 pubmed
    ..The three variants are associated with distinct types of human leukemias. Examination of the signaling pathways differentially regulated by the Bcr-Abl proteins will help us gain better insight into Bcr-Abl mediated leukemogenesis. ..
  45. Li J, Wu W, Wang Z, Sun G. Apoptotic effect of As2S2 on K562 cells and its mechanism. Acta Pharmacol Sin. 2002;23:991-6 pubmed
    ..The decline of the Bcr-Abl protein and its PTK activity may play an important role in the apoptotic effect of As2S2. As2S2 may be a useful agent for the treatment of CML. ..
  46. Szatrowski T, Dodge R, Reynolds C, Westbrook C, Frankel S, Sklar J, et al. Lineage specific treatment of adult patients with acute lymphoblastic leukemia in first remission with anti-B4-blocked ricin or high-dose cytarabine: Cancer and Leukemia Group B Study 9311. Cancer. 2003;97:1471-80 pubmed
    ..Intensification therapy with anti-B4-blocked ricin is feasible for patients with CD19 positive ALL, although there is little evidence of an additional clinical benefit from the anti-B4-blocked ricin. Cancer 2003;97:1471-80. ..
  47. Nardi V, Azam M, Daley G. Mechanisms and implications of imatinib resistance mutations in BCR-ABL. Curr Opin Hematol. 2004;11:35-43 pubmed
    ..Insights into the emerging problem of resistance should promote the rational development of alternative, synergistic, and potentially curative treatment strategies. ..
  48. Ito T. [CML with mu-BCR/ABL mRNA: clinical characteristics of our three cases and 26 reported cases]. Rinsho Ketsueki. 2003;44:234-41 pubmed
  49. Huang M, Hu Z, Chang W, Ou D, Zhou J, Zhang Y. The growth factor independence-1 (Gfi1) is overexpressed in chronic myelogenous leukemia. Acta Haematol. 2010;123:1-5 pubmed publisher
    ..The expression of Gfi1 was correlated with BCR/ABL significantly. Gfi1 may be implicated in the pathogenesis of CML and can serve as a potential target for the management of the disease. ..
  50. Zagaria A, Anelli L, Albano F, Vicari L, Schiavone E, Annunziata M, et al. Molecular cytogenetic characterization of deletions on der(9) in chronic myelocytic leukemia. Cancer Genet Cytogenet. 2006;167:97-102 pubmed
    ..Our study shows that the location of the deleted sequences was downstream of the ABL gene and that genomic microdeletions were concomitant with the ins(9;22)(q34;q11q11) rearrangement. ..
  51. Cohen N, Rozenfeld Granot G, Hardan I, Brok Simoni F, Amariglio N, Rechavi G, et al. Subgroup of patients with Philadelphia-positive chronic myelogenous leukemia characterized by a deletion of 9q proximal to ABL gene: expression profiling, resistance to interferon therapy, and poor prognosis. Cancer Genet Cytogenet. 2001;128:114-9 pubmed
    ..This finding may identify a sub-group of CML patients with different cell properties and a relatively poor prognosis. ..
  52. Huntly B, Shigematsu H, Deguchi K, Lee B, Mizuno S, Duclos N, et al. MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors. Cancer Cell. 2004;6:587-96 pubmed
    ..These data demonstrate that some, but not all, leukemia oncogenes can confer properties of leukemic stem cells to hematopoietic progenitors destined to undergo apoptotic cell death. ..
  53. Scaife R, Job D, Langdon W. Rapid microtubule-dependent induction of neurite-like extensions in NIH 3T3 fibroblasts by inhibition of ROCK and Cbl. Mol Biol Cell. 2003;14:4605-17 pubmed