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
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.