TY - JOUR
T1 - Flow cytometric immunophenotypic alterations of persistent clonal haematopoiesis in remission bone marrows of patients with NPM1-mutated acute myeloid leukaemia
AU - Loghavi, Sanam
AU - DiNardo, Courtney D.
AU - Furudate, Ken
AU - Takahashi, Koichi
AU - Tanaka, Tomoyuki
AU - Short, Nicholas J.
AU - Kadia, Tapan
AU - Konopleva, Marina
AU - Kanagal-Shamanna, Rashmi
AU - Farnoud, Noushin R.
AU - Pierce, Sherry
AU - Khoury, Joseph D.
AU - Jorgensen, Jeffrey L.
AU - Patel, Keyur P.
AU - Daver, Naval
AU - Yilmaz, Musa
AU - Medeiros, L. Jeffrey
AU - Kantarjian, Hagop
AU - Ravandi, Farhad
AU - Wang, Sa A.
N1 - Publisher Copyright:
© 2021 British Society for Haematology and John Wiley & Sons Ltd
PY - 2021/3
Y1 - 2021/3
N2 - 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 (NPM1mut) AML, we identified 50 who achieved NPM1mut 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 NPM1mut 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).
AB - 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 (NPM1mut) AML, we identified 50 who achieved NPM1mut 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 NPM1mut 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).
KW - AML
KW - Clonal hematopoiesis
KW - MRD
KW - NPM1
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U2 - 10.1111/bjh.17347
DO - 10.1111/bjh.17347
M3 - Article
C2 - 33618432
AN - SCOPUS:85101008066
SN - 0007-1048
VL - 192
SP - 1054
EP - 1063
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 6
ER -