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Despite the study of BCR::ABL1-positive and -negative myeloproliferative neoplasms (MPNs) providing seminal insights into cancer biology, tumor evolution and precision oncology over the past half century, significant challenges remain. MPNs are clonal hematopoietic stem cell-derived neoplasms with heterogenous clinical phenotypes and a clonal architecture which impacts the often-complex underlying genetics and microenvironment. The major driving molecular abnormalities have been well characterized, but debate on their role as disease-initiating molecular lesions continues.

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Exploring treatment-driven subclonal evolution of prognostic triple biomarkers: Dual gene fusions and chimeric RNA variants in novel subtypes of acute myeloid leukemia patients with KMT2A rearrangement.

Drug Resist Updat

January 2025

Loma Linda University Cancer Center, Loma Linda, CA 92354, United States; Department of Basic Sciences, Loma Linda University, Loma Linda, CA 92354, United States. Electronic address:

Chromosomal rearrangements (CR) initiate leukemogenesis in approximately 50 % of acute myeloid leukemia (AML) patients; however, limited targeted therapies exist due to a lack of accurate molecular and genetic biomarkers of refractory mechanisms during treatment. Here, we investigated the pathological landscape of treatment resistance and relapse in 16 CR-AML patients by monitoring cytogenetic, RNAseq, and genome-wide changes among newly diagnosed, refractory, and relapsed AML. First, in FISH-diagnosed KMT2A (MLL gene, 11q23)/AFDN (AF6, 6q27)-rearrangement, RNA-sequencing identified an unknown CCDC32 (15q15.

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Bosutinib for the Treatment of CML-Using it Safely: a Podcast.

Target Oncol

January 2025

Division of Hematology and SCT, Georgia Cancer Centre, Augusta, GA, USA.

Bosutinib is a second-generation tyrosine kinase inhibitor (TKI) approved for use in patients with newly diagnosed Philadelphia chromosome (Ph)-positive chronic phase (CP) chronic myeloid leukemia (CML), as well as Ph-positive CP, accelerated phase, or blast phase (with chemotherapy) CML resistant or intolerant to prior therapy. Clinical trials have shown bosutinib is effective as first-line therapy for patients with CML as well as in later lines of therapy after prior TKI failure. Bosutinib has an established safety profile; however, as with all TKIs approved for the treatment of CML, there are adverse events (AEs) that require management.

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PurposeChimeric antigen receptor (CAR) T-cell CD19 therapy has changed the treatment paradigm for patients with relapsed/refractory B-cell acute lymphoblastic leukemia. It is frequently associated with potentially severe toxicities: cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and admission to PICU is often required. Some biomarkers seem to correlate with CRS severity.

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The chronic myeloid leukemia (CML) is easily diagnosed by laboratory examination, however, rare BCR-ABL1 mRNA transcripts variants, such as e1a3 present diagnosis and therapeutic challenges. This case report details the diagnosis and management of a CML patient with the e1a3 transcript by FISH and RT-PCR. Following initial diagnosis, the patient was treated with the tyrosine kinase inhibitor (TKI) Flumatinib.

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