期刊
BRITISH JOURNAL OF HAEMATOLOGY
卷 192, 期 6, 页码 1054-1063出版社
WILEY
DOI: 10.1111/bjh.17347
关键词
Clonal hematopoiesis; AML; MRD; NPM1
类别
Persistent clonal hematopoiesis (CH) in patients with acute myeloid leukemia (AML) after achieving NPM1(mut) clearance is common and may lead to immunophenotypic changes in myeloid progenitors. It is crucial not to misinterpret these cells as AML measurable residual disease (MRD).
Clonal haematopoiesis (CH) in patients with acute myeloid leukaemia (AML) may persist beyond attaining complete remission. From a consecutive cohort of 67 patients with nucleophosmin 1-mutated (NPM1(mut)) AML, we identified 50 who achieved NPM1(mut) clearance and had parallel multicolour flow cytometry (MFC) and next generation sequencing (NGS). In total, 13 (26%) cleared all mutations, 37 (74%) had persistent CH frequently involving DNA methyltransferase 3 alpha (DNMT3A,70%), tet methylcytosine dioxygenase 2 (TET2, 27%), isocitrate dehydrogenase 2 (IDH2, 19%) and IDH1 (11%). A small number (<1%) of aberrant CD34(+) myeloblasts, but immunophenotypically different from original AML blasts [herein referred to as a pre-leukaemic (PL) phenotype], was detected in 17 (49%) patients with CH, but not in any patients with complete clearance of all mutations (P = 0 center dot 0037). A PL phenotype was associated with higher mutation burden (P = 0 center dot 005). Persistent IDH2 and serine and arginine-rich splicing factor 2 (SRSF2) mutations were exclusively observed in PL+ CH+ cases (P = 0 center dot 016). Persistent dysplasia was seen exclusively in cases with a PL+ phenotype (29% vs. none; P = 0 center dot 04). The PL+ phenotype did not correlate with age, intensity of induction therapy or relapse-free survival. Post-remission CH in the setting of NPM1(mut) clearance is common and may result in immunophenotypic changes in myeloid progenitors. It is important to not misinterpret these cells as AML measurable residual disease (MRD).
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