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Flow cytometric immunophenotypic alterations of persistent clonal haematopoiesis in remission bone marrows of patients with NPM1 ‐mutated acute myeloid leukaemia
Author(s) -
Loghavi Sanam,
DiNardo Courtney D.,
Furudate Ken,
Takahashi Koichi,
Tanaka Tomoyuki,
Short Nicholas J.,
Kadia Tapan,
Konopleva Marina,
KanagalShamanna Rashmi,
Farnoud Noushin R.,
Pierce Sherry,
Khoury Joseph D.,
Jorgensen Jeffrey L.,
Patel Keyur P.,
Daver Naval,
Yilmaz Musa,
Medeiros L. Jeffrey,
Kantarjian Hagop,
Ravandi Farhad,
Wang Sa A.
Publication year - 2021
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.17347
Subject(s) - npm1 , idh1 , myeloid , minimal residual disease , idh2 , immunophenotyping , dysplasia , haematopoiesis , cd34 , bone marrow , medicine , basophilia , isocitrate dehydrogenase , immunology , flow cytometry , cancer research , mutation , biology , karyotype , stem cell , genetics , biochemistry , gene , chromosome , enzyme
Summary 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 3α ( 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 = 0·0037). A PL phenotype was associated with higher mutation burden ( P = 0·005). Persistent IDH2 and serine and arginine‐rich splicing factor 2 ( SRSF2 ) mutations were exclusively observed in PL + CH + cases ( P = 0·016). Persistent dysplasia was seen exclusively in cases with a PL + phenotype (29% vs. none; P = 0·04). 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).