A comparative analysis of the clinical and genetic profiles of blast phase BCR::ABL1-negative myeloproliferative neoplasm and acute myeloid leukemia, myelodysplasia-related

IF 2.2 4区医学 Q3 HEMATOLOGY International Journal of Laboratory Hematology Pub Date : 2024-04-26 DOI:10.1111/ijlh.14280

Dong Chen, Julia Geyer, Adam Bagg, Robert Hasserjian, Olga K. Weinberg

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引用次数: 0

Abstract

Introduction

The classic Philadelphia chromosome–negative myeloproliferative neoplasms (Ph (-) MPNs), have variable potential for progression to the blast phase (MPN-BP) of the disease. Except initiated by distinct driver mutations, MPN-BP frequently carry similar genetic abnormalities defining acute myeloid leukemia myelodysplasia-related (AML-MR). Because of dissimilar initial pathogenesis, MPN-BP and AML-MR are retained under different disease categories. To determine if separately classifying these entities is justified, we compare MPN-BP with AML-MR patients based on mutational landscape and clinical parameters.

Methods

104 MPN-BP patients and 145 AML-MR patients were identified with available clinical, cytogenetic, and genetic data.

Results

AML-MR patients presented with a higher blast count (median, 51% vs. 30%) while MPN-BP patients had higher WBC counts, platelet counts and bone marrow cellularity (all p<0.0001). Patients with MPN-BP showed similar genetic mutations with similar mutation pattern (functional domain, hotspot and locus involved by the mutations) but a different mutation rate from AML-MR, with more frequent JAK2, CALR, MPL, ASXL1, IDH2, SETBP1 and SRSF2 mutations and less frequent TP53 and DNMT3A mutations. The overall survival (OS) of MPN-BP (OS post-BP-progression) is comparable to that of AML-MR (median OS, 9.5 months vs. 13.1 months, p=0.20). In addition, the subgroups of MPN-BP show similar OS as AML-MR. When harboring certain mutation such as TP53, ASXL1, DNMT3A, TET2, RUNX1, IDH1, IDH2, EZH2, U2AF1, BCOR and SRSF2, MPN-BP and AML-MR patients carrying the same somatic mutation show no difference in OS.

Conclusion

MPN-BP and AML-MR harbor similar somatic mutations and clinical outcomes, suggesting a unified clinical disease entity.

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胚泡期BCR::ABL1阴性骨髓增生性肿瘤和骨髓增生异常相关急性髓性白血病的临床和遗传特征对比分析。

导言：典型的费城染色体阴性骨髓增殖性肿瘤（Ph (-) MPNs）有不同的潜能发展到疾病的爆发期（MPN-BP）。除了由不同的驱动基因突变引发外，MPN-BP 经常携带与急性髓性白血病骨髓增生异常相关（AML-MR）类似的基因异常。由于初始发病机制不同，MPN-BP 和 AML-MR 被归入不同的疾病类别。为了确定将这两种疾病分开分类是否合理，我们根据突变情况和临床参数对 MPN-BP 和 AML-MR 患者进行了比较。结果AML-MR 患者的胚泡计数较高（中位数为 51% 对 30%），而 MPN-BP 患者的白细胞计数、血小板计数和骨髓细胞数都较高（均 p<0.0001）。MPN-BP 患者的基因突变相似，突变模式（功能域、热点和突变涉及的位点）相似，但突变率与 AML-MR 不同，JAK2、CALR、MPL、ASXL1、IDH2、SETBP1 和 SRSF2 突变较多，而 TP53 和 DNMT3A 突变较少。MPN-BP的总生存期（OS）（BP进展后的OS）与AML-MR相当（中位OS，9.5个月对13.1个月，P=0.20）。此外，MPN-BP 亚组的 OS 与 AML-MR 相似。当MPN-BP和AML-MR携带某些突变时，如TP53、ASXL1、DNMT3A、TET2、RUNX1、IDH1、IDH2、EZH2、U2AF1、BCOR和SRSF2，携带相同体细胞突变的MPN-BP和AML-MR患者的OS没有差异。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Laboratory Hematology 医学-血液学

CiteScore

4.50

自引率

6.70%

发文量

211

审稿时长

6-12 weeks

期刊介绍： The International Journal of Laboratory Hematology provides a forum for the communication of new developments, research topics and the practice of laboratory haematology. The journal publishes invited reviews, full length original articles, and correspondence. The International Journal of Laboratory Hematology is the official journal of the International Society for Laboratory Hematology, which addresses the following sub-disciplines: cellular analysis, flow cytometry, haemostasis and thrombosis, molecular diagnostics, haematology informatics, haemoglobinopathies, point of care testing, standards and guidelines. The journal was launched in 2006 as the successor to Clinical and Laboratory Hematology, which was first published in 1979. An active and positive editorial policy ensures that work of a high scientific standard is reported, in order to bridge the gap between practical and academic aspects of laboratory haematology.