ABL1 expression

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.

Furthermore, the proliferation-inhibited function of PHF8-knockdown have stronger effect on imatinib mesylate (IM)-resistant CML cells. Mechanistically, we identified that PHF8 as a transcriptional modulator interacted with the promoter of the BCR::ABL1 fusion gene and alters the methylation levels of H3K9me1, H3K9me2 and H3K27me1, thereby promoting BCR::ABL1 transcription. Overall, our study suggests that targeting PHF8, which directly regulates BCR::ABL1 expression, is a useful therapeutic approach for CML.

Furthermore, digital PCR for both BCR::ABL1 expression and ABL1 mutations were conducted in a sub-cohort. This manuscript describes and discusses the clinical importance and relevance of molecular biology testing in Brazilian CML patients, demonstrating its cost-effectiveness.

Our findings suggest an early, sustained, and angiogenesis-independent autocrine role for ANGPTL4 in HNSCC progression and expose ANGPTL4/NRP1/ABL1/PXN as an early molecular marker and vulnerable target for the prevention of HNSCC growth and metastasis.

In a comparative expression analysis, the expression of BCR-ABL1 is onefold high in AML, but four- and sevenfold high in ALL and CML, respectively, as compared with normal levels. In this study, a significant difference was observed in the expression levels of BCR-ABL1 between CML (p = 0.0043) and ALL (p = 0.0006) and between CML and AML groups, and a high expression of BCR-ABL1 was noted in CML as compared with ALL and AML.

Additional in silico molecular docking studies revealed binding modes and affinities of curcumin with different targets and the results are in accordance with in vitro findings. Altogether, these results indicate the potential role of curcumin in the treatment of CML.

Conversely, our data showed that miR-495-3p overexpression hindered leukemic cell growth and TKI resistance even in Imatinib-resistant T315I-mutant cells as well as drug efflux activity through MDR1 regulation. To further investigate the role of miR-495-3p in CML patients, we found that predicted miR-495-3p targets were upregulated in patients in blast crisis involved in protein phosphorylation and associated with the worst prognosis. Taken together, our results demonstrate that down-regulation of miR-495-3p expression is important in the malignant phenotype of CML and TKI resistance mechanisms, which could be a useful biomarker and a potential therapeutic target to eradicate CML.

Outcomes on generic imatinib were comparable to branded imatinib. However, nilotinib showed superiority over imatinib, especially in patients whose start of treatment was delayed.

The same trend was found both for imatinib and 2G-TKIs. A receiver operating characteristic (ROC) analysis to determine a threshold value of BCR::ABL1 at 1 month after discontinuation identified a cut-off value of 0.0051%, with 92.2% specificity, 31.7% sensitivity and a likelihood ratio of 4.087.

We counted the existing drugs targeting ABL1, which indicates that inhibiting ABL1 expression may improve the survival probability of HCC. In conclusion, ABL1 plays a crucial role in the development and progression of this cancerization and is a potential drug target.

SFPQ-ABL1 was sensitive to navitoclax and S-63845 and promotes cell survival by maintaining expression of Mcl-1 and Bcl-xL. SFPQ-ABL1 was sensitive to navitoclax and S-63845 and promotes cell survival by maintaining expression of Mcl-1 and Bcl-xL. SFPQ-ABL1 has functionally distinct mechanisms by which it drives ALL, including subcellular localisation, proliferative capacity, and activation of cellular pathways, highlighting the role that fusion partners have in mediating the function of ABL1 fusions.

However, we describe another specific ABL kinase inhibitor, possessing physicochemical characteristics suitable for BBB penetration, and which after administration (either i.v., i.p. or p.o.) to mice achieves substantial, pharmacologically relevant brain concentrations. This bipyridine compound (4) therefore has potential for elucidating the role of ABL kinases in the brain in non-clinical studies.

Both methods demonstrated diagnostic specificity of 100% and while diagnostic sensitivity reaches more than 90% in samples with RT-qPCR cycle threshold above 31. The obtained data indicates that the proposed method here described is a cheaper, robust and specific approach for CML diagnosis with outstanding performance, especially for CML diagnostic procedure where present high BCR-ABL1 expression.

Moreover, treatment with Chb-M' consistently downregulated the expression of BCR-ABL1 in these cells and this drug was highly effective even in an imatinib-resistant Ph ALL cell line...In summary, targeting RUNX1 therapeutically in Ph ALL cells may lead to overcoming TKI resistance through the transcriptional regulation of BCR-ABL1. Chb-M' could be a novel drug for patients with TKI-resistant refractory Ph ALL.

Phosphorylation of P was specifically inhibited after the incubation of BCR-ABL1 positive cell lysates with imatinib, but not with ruxolitinib. While requiring further optimization and validation in leukemic blasts to be of clinical interest, the P-based ELISA assay provides a novel in vitro tool for screening both the aberrant ABL1 activity in BCR-ABL1 like ALL leukemic cells and their potential response to TK inhibitors.

The patient started oral imatinib 400 mg per day and achieved a complete cytogenetic response at 3 months...Then the patient was started on treatment for ISS stage II standard risk myeloma with ID regimen: ixazomib 4 mg on days 1, 8 , 15 and dexamethasone 20 mg on days 1, 8, 15 , 22 in 28-day cycles...N1 Shangcheng Road. Yiwu, Zhejiang, Peoples R China.

Furthermore, ABL1 expression was positively associated with the expression levels of immune checkpoint genes, such as PD-1L, TIM3, TIGIT, and CTLA4. ABL1 is associated with immune infiltration and prognosis of HCC.

As a result, RAG expressing BCR-ABL1 cells decrease sensitivities to tyrosine kinase inhibitors (TKIs) by activating BCR-ABL1 signaling but independent of the levels of BCR-ABL1 expression and mutations in BCR-ABL1 tyrosine kinase domain. These findings identify a surprising and novel role of RAG in the functional specialization of disease progression in BCR-ABL1 leukemia through its endonuclease activity.

Therefore, the ABL1-MS1 region can affect ABL1 expression of bladder cancer. This study provides that ABL1-MS1 can be used as a DNA fingerprinting marker. In addition, rare allele detection can predict susceptibility to bladder cancer.

The objective of this paper is to describe how we select ponatinib dosage for CML patients in chronic phase in our clinical practice based on the available evidence and our clinical experience. We propose dosing regimens for the optimal starting dose for six generic cases of CML patients in chronic phase eligible for the switch to ponatinib and provide an algorithm to guide ponatinib dosing during treatment.

The present work proves that the disease-inducing potential of BV-173 and RCH-ACV leukemic cells xenografted to SCID mouse peritoneum differs between cell lines, depending on cell number, type, status, and cytogenetic disease profile when ovarian tissue is harvested.

Metabolic vulnerabilities in LSCs open the road for new therapeutic strategies. This is the first report of the miRNome of CML-CP CD34CD38 fractions that distinguishes between CD26 (BCR-ABL1 ) and their CD26 (BCR-ABL1 ) counterparts, providing valuable data for future studies.