ABL1 deletion

We determined that the microfluidic chip assay to detect CALR exon 9 mutations was acceptable for clinical use. Compared with the conventional method, the microfluidic analysis assay benefits from a streamlined workflow, faster turnaround, and a smaller instrument footprint.

The patient was started on nilotinib therapy...This case pinpoints the importance of comprehensive study when MDS is present with deletion 20q and a t(9;22), as it can be misdiagnosed as CML. While definitive therapeutic guidelines have yet to be established for this rare presentation of MDS, the use of tyrosine kinase inhibitors is under investigation.

In addition, the deletion of Tif1β sensitized BCR::ABL1 KI leukemic cells to dasatinib...TIF1β directly bound to the promoters of proliferation genes, such as FOSL1, in human BCR::ABL1 cells, in which TIF1β and FOSL1 bound to adjacent regions of chromatin. Since the expression of Fosl1 was critical for the enhanced growth of BCR::ABL1 KI cells, Tif1β and Fosl1 interacted to activate the leukemic transcriptional program in and cellular function of BCR::ABL1 KI stem cells and drove the progression of myeloid leukemia.

After considering transplantation, high ECM1 transcription level was not an independent risk factor, although OS was still poor (low vs. high, 71.1% vs. 56.8%, P = 0.038). Our findings suggested that ECM1 may be a potential molecular marker for diagnosis, minimal residual disease (MRD) monitoring, and prognosis prediction of B cell ALL.Trial registration Trial Registration Registered in the Beijing Municipal Health Bureau Registration N 2007-1007 and in the Chinese Clinical Trial Registry [ChiCTR-OCH-10000940 and ChiCTR-OPC-14005546]; http://www.chictr.org.cn .

Additionally, somatic lesions involving ZEB2, SETD2, SH2B3, and CRLF2, were associated with reduced ex vivo imatinib sensitivity. Our data suggest that the poor prognostic value of IKZF1(plus) deletions is linked to intrinsic mechanisms of TKI resistance other than ABL1 kinase domain mutations in newly diagnosed pediatric and adult BCR::ABL1-positive BCP-ALL.

In both cases, the disease was refractory to multiple agents in the recurrent phase after allogeneic hematopoietic cell transplantation. This is a case report of a truncated ABL1 mutation in 2 patients with Ph B-ALL.

The logistics of proceeding to transplant might necessitate consolidation chemotherapy usually involving high dose cytarabine (HiDAC)...Infections included bacteremia from Klebsiella, E. Coli, Proteus, group B strep, vancomycin resistant E. Faecalis, and coagulase negative staph, pneumonia from Klebsiella, urinary tract infections from extended spectrum beta-lactamase resistant E. Coli, Klebsiella, and proteus mirabilis, fungal sinusitis, and Clostridium difficile colitis...HSCT is the sole curative option for high-risk AML patients, and the concept of bridging the period between induction and HSCT with HiDAC consolidation appears to offer no additional benefit compared to IDAC. Moreover, this approach prevents a subset of this population from being fit enough to receive HSCT.

With >2 years of follow-up in the phase 3 ASCEMBL study, asciminib (ASC) has continued to demonstrate superior efficacy vs bosutinib (BOS) in pts with CML-CP after ≥2 prior TKIs, and analysis of cancer gene somatic mutations in this population has the potential to reveal additional insights into pts' response to study treatments or characteristics of the disease in later lines of therapy... Adults with CML-CP previously treated with ≥2 TKIs with intolerance of their last TKI or lack of efficacy per 2013 European LeukemiaNet recommendations and without BCR::ABL1 T315I or V299L mutations were randomized 2:1 to ASC 40 mg twice daily or BOS 500 mg once daily... ASXL1 mutations are most frequently detected at CML diagnosis and were enriched at BL in this study of pts with CML-CP previously treated with ≥2 TKIs, which is consistent with a role in TKI resistance. RUNX1 and IKZF1 mutations, which are associated with progression to accelerated or blast phase in CML, were very rare in this pt population, supporting their role in CML disease progression. The high frequency of co-occurrence of BCR::ABL1 mutations and blood cancer gene mutations in CML-CP is an important finding since cancer gene mutations could modify response to TKIs in individual pts.

This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No IMI001-07. The JU receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA.