BCR-ABL1 fusion

At the time of initial diagnosis, the patient presented with a primary tumor in the right thigh and extensive metastatic involvement affecting both lungs, pleura, mediastinum, pelvic cavity, and the right inguinal region, resulting in the classification of the case as high-risk. In addition to conventional multimodal therapy, early intervention using tyrosine kinase inhibitors was implemented, leading to the achievement of an early complete response.

In the present study, Imatinib-sensitive K-562S cells were subjected to CBD treatment (IC50: 17.69 μM) for 4 and 12 h, followed by RNA sequencing to identify differentially expressed genes (DEGs)...The results presented in this study validate the considerable potential of CBD to induce broad transcriptional and signalling alterations, related to immune modulation, apoptosis, and metabolic processes in K-562S cells. These findings provide novel insights into the therapeutic potential of CBD and lay the groundwork for further investigation into its precision applications in haematological malignancies.

In the second case, a previously undetected BCR-ABL1 fusion was identified in a relapsed AML patient, along with additional molecular lesions, underscoring the aggressive nature of the disease. Our findings support a systematic, multimodal screening strategy in patients with atypical presentations to ensure the timely detection of clinically actionable fusion events.

In this study, we employed molecular dynamics simulation to observe the synergistic interactions of BCR-ABL1 by the allosteric inhibitor asciminib and ATP competitive inhibitors nilotinib and ponatinib. Our study reveals the allosteric communication pathway between asciminib and ponatinib, providing more detailed insights into the effectiveness of combination therapy. These findings provide valuable insights into combination therapies, aiding in the rational use of medications and guiding the design of novel inhibitors.

Tyrosine kinase inhibitors (TKIs), including imatinib and dasatinib, remain cornerstone treatments; however, marked inter‑variant heterogeneity in TKI responsiveness is observed: Patients harboring e13a3/e14a3 transcripts generally show favorable prognoses, while those with e1a3/e6a2 variants demonstrate an increased risk of relapse and/or TKI resistance, often requiring multimodal strategies combining chemotherapy or allogeneic hematopoietic stem cell transplantation. Despite advances in elucidating the clinical implications of fusion gene heterogeneity in leukemogenesis, the prognostic value of atypical BCR‑ABL1 isoforms requires further validation through multicenter studies with extended cohorts. This review aimed to summarize cases of atypical fusion genes in CML, with analysis of clinical characteristics, therapeutic interventions, and prognostic outcomes, to provide clinicians with enhanced reference material for improved patient management.

The first of these was imatinib, which was released in 2001...However, a subset of the responders may achieve treatment-free remission (TFR) without ongoing therapy. For those individuals who are in the advanced state of the disease, do not respond to the TKI drugs or cannot tolerate them, allogeneic hematopoietic stem cell transplantation (SCT) is an alternative therapy that can achieve long-term survival in some cases.

Notably, curcumin derivatives such as pentagamavunon-1 (PGV-1) and compound 1206 (C1206) displayed enhanced potency and overcame resistance in imatinib-resistant CML cells...Its ability to sensitize resistant cells and enhance apoptotic pathways positions it as a promising adjunct to current CML therapies. However, clinical translation requires further investigation to overcome pharmacokinetic limitations and validate efficacy in vivo.

Imatinib, the first BCR:ABL1 tyrosine kinase inhibitor (TKI), significantly improved survival, and was followed by more potent TKIs (dasatinib, nilotinib, and ponatinib) with activity also against resistance mutations. The introduction of blinatumomab, a CD19-CD3 bispecific T-cell engager, has further transformed the treatment of Ph+ ALL, allowing some patients to be treated without cytotoxic chemotherapy and/or HSCT...Ongoing investigation focuses on more accurately identifying clinical and genetic features which predict for systemic or central nervous system relapse and determining the most effective approach to successfully risk-adapt therapy, including appropriate allocation to HSCT. This review highlights recent advances in treatment, emphasizing the importance of TKIs, the emerging role of immunotherapy, and the evolving position of HSCT in the management of Ph+ ALL.

The BCR-ABL1 fusion gene and t (16;22) are rare in chronic myeloid leukemia, easily resistant to imatinib, and complex chromosomal translocations have great influence on the curative effect and prognosis.

It underscores the importance of using multiple complementary molecular diagnostic techniques when evaluating disease progression in myeloproliferative neoplasms. Early recognition of such atypical transformations is essential, as it can open the door to targeted therapies that may significantly alter the patient's prognosis and clinical trajectory.

Such complex cases are rarely reported. Here we discuss the diagnosis and treatment of CMML transformed into AML as well as the rarity of cardiac myeloid sarcomas with an in-depth literature review.

Genetic abnormalities have a role in the classification, prognosis, and treatment of AML patients. However, treatment outcomes in AML are influenced by multiple factors beyond genetics, including infection-related complications, nutritional status, socioeconomic conditions, supportive care infrastructure, and access to intensive chemotherapy and transplant services. Supportive care plays an important role in the treatment outcome of childhood AML.