This study demonstrates that FAM168A may act as a linker protein that binds to BCR-ABL1 and AKT1, which further mediates the downstream signaling pathways in CML.
Our data showed that complex BCR-ABL1 signal patterns were associated with leukemic clonal evolution and poorer prognosis in BCR-ABL1 positive leukemia.
A t(9;22) chromosomal translocation which forms the chimeric tyrosine kinase breakpoint cluster region (BCR)‑Abelson murine leukemia viral oncogene homolog 1 (ABL) is a key mechanism underlying the pathogenesis of chronic myelogenous leukemia (CML).
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.
Therefore, the identification and control of downstream molecules/ signaling route of the BCR-ABL1 that are involved in the survival and self-renewal of leukemia stem cells can be an effective treatment strategy to eliminate leukemia stem cells, which supposed to be cured by Musashi2-Numb signaling pathway.
We observed higher frequency of <i>KIR A</i> homozygosity among 745 healthy Chinese Southern Han than 836 adult patients representing three types of leukemia: ALL (OR = 0.68, 95% CI = 0.52-0.89, <i>p</i> = 0.004), AML (OR = 0.76, 95% CI = 0.59-0.98, <i>p</i> = 0.034), and CML (OR = 0.72 95% CI = 0.51-1.0, ns).
BCR-ABL1 point mutation-mediated resistance to tyrosine kinase inhibitor (TKI) therapy in Philadelphia chromosome-positive (Ph<sup>+</sup>) leukemia is effectively managed with several approved drugs, including ponatinib for BCR-ABL1<sup>T315I</sup>-mutant disease.
<b>Conclusion:</b> HNRNPA1-mediated exosomal transfer of miR-320 from leukemia cells to BMMSC is an important mediator of leukemia progression and is a potential therapeutic target for CML.
CML is a highly treatable form of leukemia with multiple orally available small molecule inhibitors of the activated BCR-ABL1 (breakpoint cluster region-ABL1) kinase.
Chronic myeloid leukemia (CML) is characterized by the presence of a constitutively activated tyrosine kinase (Breakpoint Cluster Region - Abelson murine leukemia viral oncogene homolog1, BCR-ABL).
Our data indicate that SIAIS178 as efficacious BCR-ABL degrader warrants extensive further investigation for the treatment of BCR-ABL<sup>+</sup> leukemia.
In addition, to clarify whether the epigenetic silencing is affected by BCR-ABL1 inhibition, we assessed the methylation status in the patients at different time intervals following the tyrosine kinase inhibition using imatinib therapy, as the first-line treatment for this type of leukemia.
Thus, the aim of this study was to investigate the effects of Shb knockout on the development of leukemia in three additional models, that is, colony stimulating factor 3 receptor-T618I-induced neutrophilic leukemia, p190 Breakpoint cluster region-cAbl oncogene 1 tyrosine kinase-induced B-cell leukemia, and G12D-Kras-induced T-cell leukemia/thymic lymphoma.
Imatinib, a breakpoint cluster region-Abelson murine leukemia tyrosine kinase inhibitor, has revolutionized the treatment of chronic myelogenous leukemia (CML).
Fusion between breakpoint cluster region (BCR) and Abelson murine leukemia viral oncogene homolog (ABL)-1 gene gives rise to BCR-ABL protein with a constitutive tyrosine kinase activity and transforms HSCs and/or hematopoietic progenitor cells (HPCs) into disease-propagating leukemia stem cells (LSCs) in chronic myeloid leukemia (CML).
Established leukemia-specific predictive biomarkers for precision medicine include those genetic lesions such as BCR-ABL1 for Philadelphia-positive acute lymphoblastic leukemia and PML-RARα for acute promyelocytic leukemia.
Chronic myeloid leukemia (CML) is a stem cell-derived leukemia in which neoplastic cells exhibit the Philadelphia chromosome and the related oncoprotein BCR-ABL1.