AML with mutated NPM1 carrying a normal or aberrant karyotype show overlapping biologic, pathologic, immunophenotypic, and prognostic features.
Acute myeloid leukemia (AML) with mutated NPM1 usually carries normal karyotype (NK), but it may harbor chromosomal aberrations whose significance remains unclear. We addressed this question in 631 AML patients with mutated/cytoplasmic NPM1. An abnormal karyotype (AK) was present in 93 of 631 cases (14.7%), the most frequent abnormalities being +8, +4, -Y, del(9q), +21. Chromosome aberrations in NPM1-mutated AML were similar to, but occurred less frequently than additional chromosome changes found in other AML with recurrent cytogenetic abnormalities according to WHO classification. Four of the 31 NPM1-mutated AML patients karyotyped at different time points had NK at diagnosis but AK at relapse: del(9q) (n = 2), t(2;11) (n = 1), inv(12) (n = 1). NPM1-mutated AML with NK or AK showed overlapping morphologic, immunophenotypic (CD34 negativity), and gene expression profile (down-regulation of CD34 and up-regulation of HOX genes). No difference in survival was observed among NPM1-mutated AML patients independently of whether they carried a NK or an AK, the NPM1-mutated/FLT3-ITD negative cases showing the better prognosis. Findings in our patients point to chromosomal aberrations as secondary events, reinforce the concept that NPM1 mutation is a founder genetic lesion, and indicate that NPM1-mutated AML should be clinically handled as one entity, irrespective of the karyotype.
Haferlach
Claudia
C
Munich Leukemia Laboratory GmbH, Munich, Germany.
Mecucci
Cristina
C
Schnittger
Susanne
S
Kohlmann
Alexander
A
Mancini
Marco
M
Cuneo
Antonio
A
Testoni
Nicoletta
N
Rege-Cambrin
Giovanna
G
Santucci
Antonella
A
Vignetti
Marco
M
Fazi
Paola
P
Martelli
Maria Paola
MP
Haferlach
Torsten
T
Falini
Brunangelo
B
D018952:Antigens, CD34 / Q000378:metabolism*; D002869:Chromosome Aberrations; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
D018952:Antigens, CD34; D018398:Homeodomain Proteins; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3