Kim Heyjin, Lee Jin Kyung, Hong Young Jun, Kang Hye Jin, Byun Byung Hyun, Lee Seung-Sook
Department of Laboratory Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea.
Medical Science Demonstration Center, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea.
Cancers (Basel). 2025 Mar 31;17(7):1185. doi: 10.3390/cancers17071185.
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).
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.
Sixteen patients developed MN-BNHL. Among the 11 MN-BNHL patients undergoing NGS, all harbored tier 1 mutations. mutations (PPM1Dms) were most frequent (73%), followed by (46%) and (36%). PPM1Dms were significantly more prevalent than in MN-SC ( = 21), where mutations were most common (64%) ( < 0.001). PPM1Dms often co-occurred with . 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 ( = 0.0376), but this benefit was negated by the presence of mutations ( = 0.0049).
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 of and its interaction with other mutations in BNHL-related myeloid neoplasm development and prognosis.
背景/目的：骨髓肿瘤是接受细胞毒性疗法治疗的B细胞非霍奇金淋巴瘤（BNHL）患者中最常见的继发性血癌。我们旨在通过比较B细胞非霍奇金淋巴瘤后发生的骨髓肿瘤（MN-BNHL）与实体癌后发生的骨髓肿瘤（MN-SC）的特征，来描述MN-BNHL的遗传和临床病理特征。
我们回顾性分析了2008年至2023年间诊断为骨髓肿瘤患者的临床病理和遗传数据，分为MN-BNHL或MN-SC。对遗传数据缺失的可用骨髓样本进行了进一步的二代测序（NGS）分析。比较了BNHL组和实体癌组骨髓肿瘤的遗传谱。
16例患者发生MN-BNHL。在接受NGS检测的11例MN-BNHL患者中，均存在1级突变。PPM1Dms突变最为常见（73%），其次是TP53（46%）和NRAS（36%）。PPM1Dms在MN-BNHL中显著比MN-SC更普遍（n = 21），后者TP53突变最常见（64%）（P < 0.001）。PPM1Dms常与TP53共同出现。它们与先前的放射免疫疗法相关（相对风险（RR）：3.3和RR 3.57）。与没有PPM1Dms的MN-BNHL患者相比，有PPM1Dms的患者生存有所改善（P = 0.0376），但这种益处被TP53突变的存在所抵消（P = 0.0049）。
PPM1Dms是MN-BNHL的一个突出遗传特征，表明其在发展过程中与MN-SC相比具有独特作用。需要进一步研究以阐明TP53在BNHL相关骨髓肿瘤发展和预后中的精确作用及其与其他突变的相互作用。
