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AML with mutated NPM1 carrying a normal or aberrant karyotype show overlapping biologic, pathologic, immunophenotypic, and prognostic features
Open accessAbstract
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.
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Cites
Cytoplasmic Nucleophosmin in Acute Myelogenous Leukemia with a Normal Karyotype
Falini, B., Mecucci, C., Tiacci, E., Alcalay, M., Rosati, R., Pasqualucci, L., La Starza, R., Diverio, D., Colombo, E., Santucci, A., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa041974 · Cited by 1,892
Self-citationMutations and Treatment Outcome in Cytogenetically Normal Acute Myeloid Leukemia
Schlenk, R. F., Döhner, K., Krauter, J., Fröhling, S., Corbacioglu, A., Bullinger, L., Habdank, M., Späth, D., Morgan, M., Benner, A., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa074306 · Cited by 1,628
Cited by
Arber, D. A., Orazi, A., Hasserjian, R., Thiele, J., Borowitz, M. J., Le Beau, M. M., Bloomfield, C. D., Cazzola, M., & Vardiman, J. W. (2016) · Blood · doi:10.1182/blood-2016-03-643544 · Cited by 10,119
on behalf of the EuroFlow Consortium (EU-FP6, L.-C.-2.-0., van Dongen, J. J. M., Lhermitte, L., Böttcher, S., Almeida, J., van der Velden, V. H. J., Flores-Montero, J., Rawstron, A., Asnafi, V, Lécrevisse, Q., et al. (2012) · Leukemia · doi:10.1038/leu.2012.120 · Cited by 934
Paris, J., Morgan, M., Campos, J., Spencer, G. J., Shmakova, A., Ivanova, I., Mapperley, C., Lawson, H., Wotherspoon, D. A., Sepulveda, C., et al. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2019.03.021 · Cited by 502
Taussig, D. C., Vargaftig, J., Miraki-Moud, F., Griessinger, E., Sharrock, K., Luke, T., Lillington, D., Oakervee, H., Cavenagh, J., Agrawal, S. G., et al. (2010) · Blood · doi:10.1182/blood-2009-02-206565 · Cited by 366
Schnittger, S., Kern, W., Tschulik, C., Weiss, T., Dicker, F., Falini, B., Haferlach, C., & Haferlach, T. (2009) · Blood · doi:10.1182/blood-2009-03-213389 · Cited by 330
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Metadata
- Authors
- Haferlach, C., Mecucci, C., Schnittger, S., Kohlmann, A., Mancini, M., Cuneo, A., Testoni, N., Rege-Cambrin, G., Santucci, A., Vignetti, M., Fazi, P., Martelli, M. P., Haferlach, T., & Falini, B.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2009-10-01
- Volume
- 114
- Issue
- 14
- Pages
- 3024-3032
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2030497324
- Cited by
- 167
- References
- 2
- FWCI
- 8.91
- Type
- journal article
- Language
- en
- Open access
- bronze
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- The paper
- Haferlach, C., Mecucci, C., Schnittger, S., Kohlmann, A., Mancini, M., Cuneo, A., Testoni, N., Rege-Cambrin, G., Santucci, A., Vignetti, M., Fazi, P., Martelli, M. P., Haferlach, T., & Falini, B. (2009). AML with mutated NPM1 carrying a normal or aberrant karyotype show overlapping biologic, pathologic, immunophenotypic, and prognostic features. Blood. https://doi.org/10.1182/blood-2009-01-197871
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