Background/Objectives: Myeloid neoplasms are the most common secondary blood cancer in B-cell non-Hodgkin lymphoma (BNHL) patients treated with cytotoxic therapies. We aimed to characterize the genetic and clinicopathologic features of myeloid neoplasms arising after B-cell non-Hodgkin lymphoma (MN-BNHL) by comparing their features with myeloid neoplasms developing after solid cancer (MN-SC). Methods: We retrospectively analyzed the clinicopathologic and genetic data of myeloid neoplasm patients diagnosed between 2008 and 2023, categorized as MN-BNHL or MN-SC. Further NGS analysis was performed on available bone marrow samples with missing genetic data. The genetic profiles of myeloid neoplasms between BNHL and solid cancer groups were compared. Results: Sixteen patients developed MN-BNHL. Among the 11 MN-BNHL patients undergoing NGS, all harbored tier 1 mutations.PPM1Dmutations (PPM1Dms) were most frequent (73%), followed byDNMT3A(46%) andTP53(36%). PPM1Dms were significantly more prevalent than in MN-SC (n= 21), whereTP53mutations were most common (64%) (p< 0.001). PPM1Dms often co-occurred withDNMT3A. They were associated with prior radioimmunotherapy (relative risk (RR): 3.3 and RR 3.57). MN-BNHL patients with PPM1Dms exhibited improved survival compared to those without (p= 0.0376), but this benefit was negated by the presence ofTP53mutations (p= 0.0049). Conclusions: PPM1Dms are a prominent genetic feature in MN-BNHL, suggesting a distinct role in its development compared to MN-SC. Further investigation is needed to elucidate the precise contribution ofPPM1Dand its interaction with other mutations in BNHL-related myeloid neoplasm development and prognosis.
背景/目的：在接受细胞毒性治疗的B细胞非霍奇金淋巴瘤（BNHL）患者中，髓系肿瘤是最常见的继发性血液癌症。本研究旨在通过比较B细胞非霍奇金淋巴瘤后发生的髓系肿瘤（MN-BNHL）与实体癌后发生的髓系肿瘤（MN-SC）的特征，明确MN-BNHL的遗传及临床病理学特点。方法：我们回顾性分析了2008年至2023年间诊断为髓系肿瘤的患者，将其分为MN-BNHL组和MN-SC组，并收集其临床病理学及遗传学数据。对缺乏遗传数据的可用骨髓样本进行了进一步的新一代测序分析，比较了BNHL组与实体癌组髓系肿瘤的遗传谱。结果：共有16例患者发展为MN-BNHL。在接受NGS检测的11例MN-BNHL患者中，所有患者均携带1级突变。其中PPM1D突变最为常见（73%），其次是DNMT3A（46%）和TP53（36%）。与MN-SC组（n=21）相比，PPM1D突变在MN-BNHL组中的发生率显著更高（p<0.001），而MN-SC组中最常见的是TP53突变（64%）。PPM1D突变常与DNMT3A突变共存，且与既往接受过放射免疫治疗相关（相对风险分别为3.3和3.57）。携带PPM1D突变的MN-BNHL患者比未携带者生存期更长（p=0.0376），但若同时存在TP53突变，则此生存获益消失（p=0.0049）。结论：PPM1D突变是MN-BNHL的一个显著遗传特征，提示其在MN-BNHL的发生发展中可能发挥着与MN-SC不同的作用。需要进一步研究以阐明PPM1D突变在BNHL相关髓系肿瘤发生发展及预后中的确切作用及其与其他突变的相互作用。
肿瘤(癌症)患者之家