Schweneker Katrin, Lenk Miriam, Kern Wolfgang, Haferlach Claudia, Meggendorfer Manja, Pohlkamp Christian, Haferlach Torsten
MLL Munich Leukemia Laboratory, Max-Lebsche-Platz 31, 81377, Munich, Germany.
Int J Hematol. 2025 Sep 4. doi: 10.1007/s12185-025-04046-5.
Chronic myeloid leukemia (CML) and BCR::ABL1-negative MPN were thought to be mutually exclusive, but synchronous and sequential cases have been reported. We screened 35,001 patients for BCR::ABL1 fusion or JAK2, CALR, or MPL mutations to investigate the sequential development of CML and BCR::ABL1 negative-MPNs. We discovered that 5.6% had primary CML followed by BCR::ABL1-negative MPN, and 5.8% had the reverse sequence. Notably, we identified higher JAK2 variant allele frequencies (VAFs) in patients developing secondary CML. Previous MPN did not compromise the effectiveness of tyrosine kinase inhibitors (TKI) in treating secondary CML. The emergence of secondary MPN appeared to be unrelated to JAK2 VAF progression or BCR::ABL1 transcript levels. Our research indicates that newly detected leukocytosis or thrombocytosis should prompt consideration of secondary MPN. It also showed that secondary CML had no negative impact on response to therapy when patients were treated according to CML guidelines.
慢性髓性白血病（CML）和BCR::ABL1阴性骨髓增殖性肿瘤（MPN）曾被认为是相互排斥的，但已有同步和序贯发生的病例报道。我们对35001例患者进行了BCR::ABL1融合或JAK2、CALR或MPL突变检测，以研究CML和BCR::ABL1阴性MPN的序贯发展情况。我们发现，5.6%的患者先发生原发性CML，随后发展为BCR::ABL1阴性MPN，5.8%的患者则顺序相反。值得注意的是，我们在继发CML的患者中发现了更高的JAK2变异等位基因频率（VAF）。既往的MPN并不影响酪氨酸激酶抑制剂（TKI）治疗继发CML的疗效。继发MPN的出现似乎与JAK2 VAF进展或BCR::ABL1转录水平无关。我们的研究表明，新检测到的白细胞增多或血小板增多应促使考虑继发MPN。研究还表明，当按照CML指南对患者进行治疗时，继发CML对治疗反应没有负面影响。
