Rabbit Anti-Human c-Abl (a.a. 401-500) Polyclonal antibody

Background/Aim: The Philadelphia chromosome is considered the hallmark of chronic myeloid leukemia (CML). However, although most patients with CML are diagnosed with the e13a2 or e14a2 breakpoint cluster region (BCR)-Abelson 1 (ABL1) fusion transcripts, about 5% of them carry rare BCR-ABL1 fusion transcripts, such as e19a2, e8a2, e13a3, e14a3, e1a3 and e6a2. In particular, the e6a2 fusion transcript has been associated with clinically aggressive disease frequently presenting in accelerated or blast crisis phases; there is limited evidence on the efficacy of front-line second-generation tyrosine kinase inhibitors for this genotype. Case Report: We describe a case of atypical BCR-ABL1 e6a2 fusion transcript in a 46-year-old woman with CML. Results: The use of primers recognizing more distant exons from the common BCR-ABL1 breakpoint region correctly identified the atypical BCR-ABL1 e16a2 fusion transcript. Treatment with second-generation tyrosine kinase inhibitor nilotinib was effective in this patient expressing the atypical e6a2 BCR-ABL1 fusion transcript.

Chronic myeloid leukemia (CML) is induced by the BCR/ABL1 oncogene, which encodes a protein tyrosine kinase. We examined the effect of direct overexpression of the human p210(BCR/ABL1) oncoprotein in zebrafish. Humanized p210(BCR/ABL1) protein was detectable in Tg(hsp70: p210(BCR/ABL1)) transgenic zebrafish embryos and adult kidney marrow. Transgenic zebrafish developed CML, which could be induced via cells transplanted into recipients. The expression of human BCR/ABL1 promoted myeloid lineages in Tg(hsp70:p210(BCR/ABL1)) transgenic embryos. A total of 77 of 101 (76.24%) Tg(hsp70:p210(BCR/ABL1)) adult transgenic zebrafish (age 6 months-1 year) developed CML. CML in zebrafish showed a triphasic phenotype, similar to that in humans, involving a chronic phase predominantly characterized by neutrophils in various degrees of maturation, an accelerated phase with an increase in blasts and immature myeloid elements, and a blast phase with >90% blasts in both the peripheral blood and kidney marrow. Tyrosine kinase inhibitors, as the standard drug treatment for human CML, effectively reduced the expanded myeloid population in Tg(hsp70:p210(BCR/ABL1)) transgenic embryos. Moreover, we screened a library of 171 compounds and identified ten new drugs against BCR/ABL1 kinase-dependent or -independent pathways that could also reduce lcp1(+) myeloid cell numbers in Tg(hsp70:p210(BCR/ABL1)) transgenic embryos. In summary, we generated the first humanized zebrafish CML model that recapitulates many characteristics of human CML. This novel in vivo model will help to elucidate the mechanisms of CML disease progression and allow high-throughput drug screening of possible treatments for this disease.