ABL1 expression

The results showed lower expression of HOTAIR and PTGS2 in CML patients. The HOTAIR expression is inversely associated with BCR::ABL1 expression in imatinib-treated CML patients, and to PTGS2 showing that CML patients with high BCR::ABL1 expression showed reduced PTGS2 expression.

Hence, we establish the T3SS of Y. enterocolitica as a highly efficient protein translocation method for monobody delivery, enabling the selective targeting of different oncogenic signaling pathways and providing a foundation for future therapeutic application against intracellular targets.

The tyrosine kinase Abl1 is of critical importance in doxorubicin induced cardiomyopathy, and we propose its inhibition as means to diminish risk of cardiotoxicity.

v) Chemotherapy resistance: AML-cells expel PEGylated liposomal doxorubicin (PLD) through EVs thus increasing their resistance ( Hekmatirad, 2021)... EVs open the window for the future investigation of novel pathophysiological mechanisms that will improve our understanding of their role in the biology of myeloid malignancies, Moreover, they hold promise as potential biomarkers and drug carriers for cell-type specific treatment

5-fluorouracil- (5-FU-) treated bone marrow (BM) cells harvested from FVB/N-tg(ScltTA)(tetO-p210-BCR::ABL1) double-transgenic (dtg) donor mice (CD45.1+) were transplanted into lethally irradiated recipient mice (CD45.2+). One week after transplantation, tetracycline (tet) was removed from the drinking water to induce Bcr-Abl1 expression... Our study demonstrates the efficacy of ABL001 in ameliorating p210-BCR::ABL1-induced lymphoid blast crisis by specifically targeting BCR::ABL1-positive malignant stem cells and restoring normal hematopoiesis in a transgenic mouse model. These promising findings highlight the potential of ABL001 as an alternative therapeutic strategy for first-line treatment of BCR::ABL1-driven leukemia, including B-lymphoblastic blast crisis. Furthermore, since TKI treatment alone has not proven successful in patients with lymphoid blast crisis, this now opens new avenues for the in vivo-testing of novel combination treatments of ABL001 with chemotherapy or other targeting agents.

We describe here the molecular details of how signals from an oncogenic tyrosine kinase become converted into changes in gene expression that define the B-lineage leukaemia subtype Ph+B-ALL. Our work highlights the complexity of these changes by acknowledging the role of gene regulatory elements/enhancers in this process and further describe for the first time that B-ALL subtypes can be distinguished by their enhancer usage and promoter-enhancer interactions. Uncovering the precise enhancer regions for the genes deregulated in Ph+B-ALL and the TFs recruited to them may open new windows for therapeutic intervention.

By further comparing BCR::ABL1 transcript levels with BCR::ABL1 fusion gene copy numbers, it is also possible to model the differential dynamics of BCR::ABL1 expression and cell number under therapy. The developed methodology can be transferred to other biomarkers for continuous therapy monitoring.

We have previously shown that high BCR::ABL1/GUS transcripts measured at diagnosis are associated with inferior responses to standard dose Imatinib (IM)...Moreover, high BCR::ABL1 expression reduced the clonogenicity of leukemic CD34+ cells and increased their sensitivity to high doses IM but not to those of dasatinib...Interestingly, we found a direct correlation between high BCR::ABL1 levels and reduced number of quiescent leukemic cells caused by increasing their cycling. Higher BCR::ABL1 levels improving the proliferation, anti-apoptotic signaling and reducing self-renewal properties cause an increased expansion of leukemic clone.

In agreement with previous studies, our results suggest that BCR/ABL1 expression under the control of the BCR promoter may not be sufficient to induce Ph + leukemia. In the future, we would like to determine the effect of second hit deletions in vitro and further evaluate their leukemic character in in vivo settings.