In chronic myeloid leukemia (CML) two main types of messenger RNA (e14a2 and e13a2) can be produced by BCR-ABL1 gene rearrangement. Due to conflicting results, the clinical value of these transcripts remains controversial. The aim of this study was to identify associations of e14a2 and e13a2 transcripts with laboratory variables and also the response to treatment. This study included 203 adult patients with CML treated with Imatinib as first-line drug in a reference hematology center in Northeast Brazil. Clinical and laboratory data were obtained after informed consent. Samples were collected for RNA extraction and analyzed by reverse transcription-polymerase chain reaction (PCR), according to the international protocol BIOMED-1. The LeukemiaNet 2013 criteria were used to establish the molecular response. The frequency distribution of the BCR-ABL1 transcripts was e14a2 (64%), e13a2 (34%), and double positives (2%). The results showed a statistically significant association of the e14a2 transcript type with thrombocytosis (P = 0.0005) and the e13a2 with higher leukocyte count (P = 0.0491). In a subgroup of 44 patients, the molecular response to treatment with Imatinib was assessed by quantitative PCR at 3 months (BCR-ABL1 ≤ 10%), 6 months (BCR-ABL1 ≤ 1%), or 12 months (BCR-ABL1 ≤ 0.1%). Although patients with the transcript e14a2 showed higher frequency of good responses than patients with the transcript e13a2, this difference was not statistically significant. In agreement with published data, our results showed association of the BCR-ABL1 transcript e14a2 with thrombocytosis and the BCR-ABL1 transcript e13a2 with higher leukocytosis in patients with chronic myeloid leukemia.
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http://dx.doi.org/10.4238/gmr16029541 | DOI Listing |
J Mol Diagn
January 2025
Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Erlangen, Germany; Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Erlangen, Germany; Bavarian Cancer Research Center (BZKF), Erlangen, Germany. Electronic address:
Achieving a stable deep molecular response with the option to discontinue tyrosine kinase inhibitors (TKI) treatment is the new therapeutic goal for patients with chronic myeloid leukemia (CML). Several studies have shown that individuals expressing the BCR::ABL1 e14a2 transcript achieve a major molecular response more rapidly than those with the e13a2 transcript. However, technical issues may have confounded these observations, and data for pediatric patients are limited.
View Article and Find Full Text PDFHematol Rep
January 2025
Department of 1st Internal Medicine, Medical School, University of Pécs, Ifjúság Str. 13, 7624 Pécs, Hungary.
T-cell prolymphocytic leukemia (T-PLL) is a rare mature T-cell lymphoma that is usually associated with poor prognosis and short overall survival. We present a case of a 61-year-old woman presenting with T-PLL and the leukemic cells harboring (-breakpoint cluster region; -ABL protooncogene 1) fusion transcripts as the result of a variant of t(9;22)(q34;q11) called Philadelphia translocation: t(9;22;18)(q34;q11;q21). Sequencing revealed a rare transcript with an exon 6 breakpoint corresponding to e6a2 transcripts, which has thus far been reported in only 26 cases of leukemias.
View Article and Find Full Text PDFCancer Manag Res
January 2025
Medical Center of Hematology, Xinqiao Hospital, Army Medical University, Chongqing, People's Republic of China.
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.
View Article and Find Full Text PDFBr J Clin Pharmacol
December 2024
Novartis Pharma AG, Basel, Switzerland.
Aims: This study aims to evaluate the exposure-efficacy relationship of nilotinib and longitudinal BCR::ABL1 levels in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukaemia in chronic phase (CML-CP) and those who are imatinib-resistant or intolerant using a semimechanistic disease model.
Methods: The analysis included 489 CML-CP patients from 3 nilotinib trials (NCT00109707; NCT00471497; NCT01043874) with duration of follow-up ranging from 2 to 9 years. The semimechanistic disease model of CML-CP consisted of quiescent leukaemic stem cells, proliferating drug-susceptible and -resistant bone marrow cells.
Front Oncol
December 2024
Institute of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, China.
The coexistence of three or more transcripts in one patient with chronic myeloid leukemia (CML) is rarely reported. Thus, the disease progression and drug response are still unknown. This case report aimed to explore the drug response of CML with variant transcripts and to enrich the clinical treatment of rare types of CML.
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