Frequency of BCR‑ABL gene mutations in Polish patients with chronic myeloid leukemia treated with imatinib. A final report of the MAPTEST study

Lewandowski, Krzysztof; Warzocha, Krzysztof; Hellmann, Andrzej; Skotnicki, Aleksander B.; Prejzner, Witold; Foryciarz, Kajetana; Sacha, Tomasz; Gniot, Michał; Majewski, Mirosław; Solarska, Iwona; Nowak, Grażyna; Wasąg, Bartosz; Kobelski, Mikołaj; Ścibiorski, Cezary; Siemiątkowski, Marek; Lewandowska, Maria; Komarnicki, Mieczysław

doi:10.20452/pamw.843

Cited by 11 publications

(5 citation statements)

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“…IM resistance has raised great attention while prompting interest in the development of other treatment strategies, so as to achieve a cure without the requirement for the transplantation of stem cells (Hochhaus et al 2002 ; Druker et al 2006 ; Lewandowski et al 2009 ). The data of this study explore a novel molecular mechanism other than point mutations in ABL and provided us another strategy to improve the sensitivity to IM especially in those subjects with IM resistance.…”

Section: Discussionmentioning

confidence: 99%

Global identification of circular RNAs in imatinib (IM) resistance of chronic myeloid leukemia (CML) by modulating signaling pathways of circ_0080145/miR-203/ABL1 and circ 0051886/miR-637/ABL1

Yao-hua

2021

Mol Med

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Imatinib (IM), targeting of BCR-ABL1 tyrosine kinase, is currently one of the first-line choices in the treatment of chronic myeloid leukemia (CML). This study aims to explore the molecular mechanisms underlying IM resistance in CML treatment. 108 CML patients were recruited and grouped according to their sensitivity to IM as the responder group (N = 66) and the non-responder group (N = 42). Real-time quantitative PCR (RT-qPCR) was performed to evaluate the expression of candidate circular RNAs (circRNAs), microRNA (miRNAs) and messenger RNA (mRNAs). No significant difference was noted regarding demographic and clinicopathological characteristics between the responder group and the non-responder group. The expression of circ_0080145, circ_0051886 and ABL1 mRNA was significantly increased, while the expression of miR-203 and miR-637 was decreased in the non-responder group as compared with the responders. By using in-silicon analysis, it was predicted that circ_0080145 and circ_0051886 targeted miR-203 and miR-637 respectively, and ABL1 was found to be shared direct target gene of miR-203 and miR-637. Ectopic over-expression of circ_0080145 and circ_0051886 respectively reduced the expression of miR-203 and miR-637. The expression of ABL1 mRNA/protein was most upregulated in culture cells co-transfected with circ_0080145 and circ_0051886 as compared with those cells individually transfected. This study established the signaling pathways of circ_0080145/miR-203/ABL1 and circ 0051886/miR-637/ABL1. The deregulation of circ_0080145 and circ_0051886 is, at least partially, responsible for the development of IM chemoresistance in CML by regulating expression of ABL1 via modulating expression of miR-203 and miR-637.

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Section: Discussionmentioning

confidence: 99%

Global identification of circular RNAs in imatinib (IM) resistance of chronic myeloid leukemia (CML) by modulating signaling pathways of circ_0080145/miR-203/ABL1 and circ 0051886/miR-637/ABL1

Yao-hua

2021

Mol Med

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“…The most frequently found mutation was T315I (10/48; 20.83% patients); this finding is in agreement with published Latin American data 3 as well as other studies that evaluated patients from different geographic locations. 8 , 9 , 10 , 11 , 12 , 13 However, some studies did not find that this mutation was the most common 5 , 7 and one did not find this mutation at all. 6 The reason for this discrepancy among the results is still unclear, but Jabbour et al 7 argued that the increase in the frequency of T315I may have occurred due to the use of TKIs to which other mutations are sensitive or to the inclusion of patients at different stages of the disease.…”

Section: Discussionmentioning

confidence: 99%

“… 4 Among the more than 100 types of mutations in the tyrosine kinase domain, T315I is the only one that has total resistance to first- and second-generation inhibitors and is reported as the most common in several studies. 3 , 8 , 9 , 10 , 11 , 12 , 13 A third-generation inhibitor, Ponatinib (AP24534), approved by the US Food and Drug Administration (FDA), 14 shows significant activity in the presence of the T315I mutation. 15 , 16 The therapeutic strategy for patients who do not have a satisfactory response to the available TKI is hematopoietic stem cell transplantation (HSCT).…”

Section: Introductionmentioning

confidence: 99%

Mutations in the breakpoint cluster region-Abelson murine leukemia 1 gene in Brazilian patients with chronic myeloid leukemia

Costa

Pereira

kaminski

et al. 2018

Hematology, Transfusion and Cell Therapy

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IntroductionMutations in the breakpoint cluster region-Abelson murine leukemia 1 gene are the leading cause of resistance to treatment with tyrosine kinase inhibitors in chronic myeloid leukemia patients. Mutations have been detected throughout the extension of the kinase domain of this gene and it is important to investigate their positions because there may be a difference in clinical relevance.ObjectiveTo evaluate mutations in the transcripts of the BCR-ABL1 gene in Brazilian patients with chronic myeloid leukemia under tyrosine kinase inhibitor treatment in the Hospital de Clínicas of the Universidade Federal do Paraná.MethodsThis retrospective observational cross-sectional study analyzed mutation data of BCR-ABL1 gene transcripts. Three hundred and thirty peripheral blood samples from 193 patients were evaluated with the search for mutations being achieved by Sanger sequencing.ResultsSixteen mutation types were identified in 48/193 (24.87%) patients with T315I (20.83%) being the most common. Furthermore, four polymorphisms (T240T, K247R, E275E and Y275Y) were identified. The highest incidence of mutations (19/53: 35.85%) occurred in the P-loop of the tyrosine kinase domain, whereas no mutation was found in the A-loop. In 43/48 (89.58%) patients only one mutation was found and more than one mutation was found in 5/48 (10.42%). The simultaneous presence of two mutations (E189G/V299L and E255K/T315I) was observed in 2/5 patients while the different mutations were seen in sequential samples of the other three patients (Y253Y/T315I, T315I/E255K and E255K/T315I).ConclusionsThis molecular characterization contributed to the identification of the resistance profile to tyrosine kinase inhibitors in Brazilian patients, thus enabling the use of adequate therapeutic strategies in a timely manner.

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“…In 2010, the standardisation of BCR-ABL1 measurement by RQ-PCR in CML patients was carried out in eight laboratories in cooperation with the ELN [14]. The results of the BCR-ABL1 KD mutation analysis in imatinib-resistant patients were also published [96]. The RQ-PCR technique was improved by modification of the e13a2 and e14a2 transcript measurement in 2019 [97].…”

Section: Molecular Diagnosticsmentioning

confidence: 99%

Current status and achievements of Polish haemato-oncology

et al. 2021

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The number of newly diagnosed haematological malignancies in Polish adults and children is about 9,000 a year, which constitutes about 5.5% of all malignancies in the country. Adult patients with haematological malignancies are diagnosed and treated in 42 institutions in Poland. The scientific and educational support for this activity is provided under the umbrella of the Polish Society of Haematologists and Transfusiologists (PTHiT, Polskie Towarzystwo Hematologów i Transfuzjologów), the Polish Adult Leukemia Group (PALG), the Polish Lymphoma Research Group (PLRG), the Polish Myeloma Study Group (PMSG), the Polish Myeloma Consortium (PMC), and consultants in haematology. www.journals.viamedica.pl/acta_haematologica_polonica 5 Sebastian Giebel et al., Current status and achievements of Polish haemato-oncologyThe aim of this position paper is to present the current status and progress in therapy of haematological malignancies in Polish haematology adult centres, focusing on the activity of PALG, PLRG, and PMSG. The achievements of Polish haemato-oncology at the beginning of the third decade of the 21 st century are set out in this paper. Polish haemato-oncology today has an important international position based on contributions to the development of knowledge, international cooperation, and a high quality of patient care. In many instances, clinical trials run by Polish collaborative groups have influenced international standards. Polish haematologists have been the authors of treatment recommendations, and their research has indicated areas for further research.

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Frequency of BCR‑ABL gene mutations in Polish patients with chronic myeloid leukemia treated with imatinib. A final report of the MAPTEST study

Cited by 11 publications

References 28 publications

Global identification of circular RNAs in imatinib (IM) resistance of chronic myeloid leukemia (CML) by modulating signaling pathways of circ_0080145/miR-203/ABL1 and circ 0051886/miR-637/ABL1

Global identification of circular RNAs in imatinib (IM) resistance of chronic myeloid leukemia (CML) by modulating signaling pathways of circ_0080145/miR-203/ABL1 and circ 0051886/miR-637/ABL1

Mutations in the breakpoint cluster region-Abelson murine leukemia 1 gene in Brazilian patients with chronic myeloid leukemia

Current status and achievements of Polish haemato-oncology

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