CML transformation to lymphoid blast phase (BP) is associated with copy number abnormalities, characteristic of BCR-ABL1 positive acute lymphoblastic leukemia, but not of CML in the chronic phase.
Experimental and computational methods were used together to explain how mutations in the kinase domain of Abl1 lead to resistance against the most advanced drug currently in use to treat chronic myeloid leukaemia.
Chronic myeloid leukemia (CML) is a myeloid clonal proliferation disease defining by the presence of the Philadelphia chromosome that shows the movement of BCR-ABL1.
Epidemiological studies of 1,3-butadiene (BD) exposures have reported a possible association with chronic myelogenous leukemia (CML), which is defined by the presence of the t(9;22) translocation (Philadelphia chromosome) creating an oncogenic BCR-ABL fusion gene.
The possibility of tumor‑derived exosomes enrichment was confirmed, and for the first time, to the best of our knowledge, the detection of the BCR‑ABL1 transcript highlighted the presence of active leukemic cells in patients with CP‑CML.
The resistance for the tyrosine kinase inhibitors in chronic myeloid leukemia (CML) occurs mainly due to BCR/ABL1 dependent and independent mechanisms.
In this article, we report a unique patient with polycythemia vera driven by a rare complex in-frame deletion-insertion mutation in JAK2 exon 12, and CML driven by uncommon p210 e14a3 (b3a3) BCR/ABL fusion transcript.
CML-LSCs are recognized as being responsible for resistances and relapses that occur despite the advent of BCR-ABL-targeting therapies with Tyrosine Kinase Inhibitors (TKIs).
More than 95% of CML patients are diagnosed with the e13a2 or e14a2 BCR-ABL1 fusion transcripts while, in about 1% of these individuals, the break generates the e1a2 rearrangement.
Cases with a first-ever MMR (BCR-ABL1 ≤0.1%, assessed at any time during follow-up) were matched to up to 5 controls by duration of TKI therapy, volume of patients with CML at the treatment center, year of cohort entry, and age.
The marked improvement in clinical outcomes for patients with chronic myeloid leukaemia (CML) can be solely attributed to the introduction of targeted therapies against the fusion oncoprotein, BCR-ABL1.
SIGNIFICANCE: Small-molecule-induced degradation of BCR-ABL1 in CML provides an advantage over inhibition and provides insights into CML stem cell biology.
We compared leukocyte volume, conductivity and scatter (VCS) characteristics of chronic myeloid leukemia (CML), bcr-abl1-positive patients with those of non-neoplastic neutrophilia.
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.
Despite the development of selective BCR-ABL-targeting tyrosine kinase inhibitors (TKIs) transforming the management of chronic myeloid leukaemia (CML), therapy-resistant leukaemic stem cells (LSCs) persist after TKI treatment and present an obstacle to a CML cure.
In this study, we explored the feasibility of BCR-Abl siRNA therapy in CML K562 cells in vitro by employing a cationic polymer derived from cholesterol (Chol) grafted low-molecular weight polyethyleneimine (PEI).
Treatment value of second-generation BCR-ABL1 tyrosine kinase inhibitors compared with imatinib to achieve treatment-free remission in patients with chronic myeloid leukaemia: a modelling study.