BCR-ABL leukemias result from leukemic stem cell/progenitor transformation and represent an opportunity to identify epigenetic progress contributing to lineage leukemogenesis.
The BCR-ABL1 oncogene is associated with chronic myeloid leukemia (CML) pathogenesis, but the molecular mechanisms that initiate leukemogenesis are still unclear.
As mutations in STAT5B, but not STAT5A, have been frequently described in hematopoietic tumors, we used BCR/ABL as model systems to investigate the contribution of STAT5A or STAT5B for leukemogenesis.
3q26.2/EVI1 rearrangements resulting in EVI1 overexpression play an important role in leukemogenesis and are associated with treatment resistance and a poorer prognosis in patients with acute myeloid leukemia, myelodysplastic syndrome, chronic myeloid leukemia and BCR-ABL negative myeloproliferative neoplasms.
Nevertheless, functional studies would be needed to establish the biological role of AIF1L-ETV6 and ABL1-AIF1L and to determine whether they contribute to leukemogenesis and/or to the final leukemia phenotype.
Depending on the translocation breakpoint, typically a p210 BCR-ABL1 or a p190 BCR-ABL onc protein are generated; both are constitutively active tyrosine kinases that play a central role to alter signaling pathways of cell proliferation, survival, and self-renewal, leading to leukemogenesis.
In this study, we demonstrated that genomic depletion of miR-17-92 inhibited the BCR-ABL induced leukemogenesis by using a mouse model of transplantation of BCR-ABL transduced hematopoietic stem cells.
The PI3K/Akt/mTOR signaling pathway is often activated in leukemias and plays a crucial role in leukemogenesis.We analyzed the effects of three BCR-ABL1 tyrosine kinase inhibitors (TKIs), alone and in combination with a panel of selective PI3K/Akt/mTOR inhibitors, on three NUP214-ABL1 positive T-ALL cell lines that also displayed PI3K/Akt/mTOR activation.
Taken together, our data suggest that BTG1 deletions might play a role in leukemogenesis of BCP-ALL as well as of BCR-ABL1-positive MPAL and CML-BC (B-lineage).
The chimeric oncogene BCR/ABL, which is the product of reciprocal translocation between chromosomes 9 and 22, is a known molecular marker of chronic myeloid leukemia (CML), and is related to the major factors involved in leukemogenesis.
Altered expression of the anti-apoptoticBcl-xL has been correlated with BCR-ABLleukemogenesis; however, its involvement in the pathogenesis and evolution of CML has not been formally demonstrated yet.
Activation of β-catenin was linked to CML leukemogenesis and drug resistance through its BCR-ABL-dependent Y phosphorylation and impaired binding to GSK3β (glycogen synthase kinase 3β).
Our results suggest that SIRT1 is a novel survival pathway activated by BCR-ABL expression in hematopoietic progenitor cells, which promotes oncogenic transformation and leukemogenesis.
Together these data demonstrate a critical role for autophagy to mitigate cell stress, and that cells expressing the oncogenic kinase BCR-Abl appear particularly dependent on autophagy for cell survival and leukemogenesis.
Chronic myeloid leukemia (CML), characterized by the t(9;22) and BCR/ABL1 fusion, is a disease model for studying the mechanisms of genetic abnormalities in leukemogenesis.
We hypothesize that FANCD2-Ub has an important role in BCR-ABL1leukemogenesis because of its ability to facilitate the repair of numerous ROS-induced DSBs.