The expression of
- BCR-ABL is a tyrosine kinase fusion protein, and is the result of the chromosomal translocation that produces the Philadelphia chromosome1
- BCR-ABL is expressed in tumor cells, and most frequently observed in chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL), and with less frequency (0.5%-3%) in acute myeloid leukemia (AML)2-4
- BCR-ABL expressing cells have increased DNA damage and genetic aberrations2
- This is further associated with the generation of genetic instability2
- BCR-ABL is constitutively active in cancers like CML, ALL and occasionally AML, and converts ATP to ADP4-6
- BCR-ABL expression promotes tumor cell proliferation and increases their resistance to apoptosis7
- Preclinical data using a mouse model of CML have shown that BCR-ABL may lead to the premature release of myeloid cells in the bone marrow, further contributing to the pathogenesis of CML8
- Preclinical evidence suggests that inhibiting BCR-ABL expression may suppress anti-apoptotic activity and make CML cells more susceptible to apoptosis by antileukemic agents9
- In preclinical studies, inhibition of BCR-ABL and other signaling pathways, such as MAPK, have shown to enhance tumor cell regression, and promote an antitumor immune response9
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1. Talpaz M, Shah NP, Kantarjian H, et al. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med. 2006;354(24):2531-2541. 2. Burke BA, Carroll M. BCR-ABL: a multi-faceted promoter of DNA mutation in chronic myelogeneous leukemia. Leukemia. 2010;24(6):1105-1112.
3. López-Andrade B, Sartori F, Gutiérrez A, et al. Acute lymphoblastic leukemia with e1a3 BCR/ABL fusion protein. A report of two cases. Exp Hematol Oncol. 2015;5:21. doi:10.1186/s40164-016-0049-y. 4. Neuendorff NR, Burmeister T, Dörken B, Westermann J.