Leukemia is a heterogeneous disease commonly associated with recurrent chromosomal translocations that involve tyrosine kinases including BCR-ABL, TEL-PDGFRB and TEL-JAK2.
Leukemias expressing the constitutively activated tyrosine kinases (TK) BCR-ABL1 and FLT3/ITD activate signaling pathways that increase genomic instability through generation of reactive oxygen species (ROS), DNA double-strand breaks (DSB), and error-prone repair.
Leukemia stem cells contribute to drug-resistance and relapse in chronic myeloid leukemia and BCR-ABL1 inhibitor monotherapy fails to eliminate them, thereby necessitating alternate therapeutic strategies.
ABL kinase domain mutations have been implicated in the resistance to the BCR-ABL inhibitor imatinib mesylate of Philadelphia-positive (Ph+) leukemia patients.
ABL kinase inhibitors have been spectacularly successful in treating CML, but disease persistence and acquired drug resistance can prevent eradication and cure of the leukemia.
BCR-ABL-dependent pre/pro-B cell lines could be established at low frequency from progenitors that lacked these genes, but the cells were smaller, proliferated more slowly, and failed to cause leukemia in vivo.
BCR-ABL caused by the translocation of t(9,22) with elevated tyrosine-kinase activity could induce leukemia in mice, which established BCR-ABL as the molecular pathogenic event in CML (Chronic myeloid leukemia).
BCR-ABLleukemias result from leukemic stem cell/progenitor transformation and represent an opportunity to identify epigenetic progress contributing to lineage leukemogenesis.
BCR-ABL is a chimeric oncoprotein that exhibits deregulated tyrosine kinase activity and is implicated in the pathogenesis of Philadelphia chromosome (Ph1)-positive human leukemias.
A complete molecular response (CMR; no detectable BCR-ABL mRNA) represents a deeper level of response, but even CMR is not a guarantee of elimination of the leukaemia, because the significance of CMR is determined by the detection limit of the assay that is used.
A novel Wnt/β-catenin signaling modulator, C82, and nilotinib synergistically killed KBM5<sup>T315I</sup> and TKI-resistant primary BC-CML cells with or without BCR-ABL kinase mutations even under leukemia/MSC co-culture conditions.
Abelson interactor protein-1 (ABI1) is a promising candidate tumor suppressor, and plays critical roles both in the pathogenesis of BCR-Abl-induced leukemia and in the spread of several solid tumors.
Activation of the abl gene and its involvement in human leukemia is one of the most thoroughly characterized examples of the structural alterations of chromosomes associated with the conversion of a normal cell into a cancer cell.
Alternative BCR/ABL splice variants in Philadelphia chromosome-positive leukemias result in novel tumor-specific fusion proteins that may represent potential targets for immunotherapy approaches.