Abstract |
Chronic myeloid malignancies are categorized to the three main categories myeloproliferative neoplasms (MPNs), myelodysplastic syndromes (MDSs) and MDS/MPN overlap. So far, no specific genetic alteration profiles have been identified in the MDS/MPN overlap category. Recent studies identified mutations in SET- binding protein 1 (SETBP1) as novel marker in myeloid malignancies, especially in atypical chronic myeloid leukemia (aCML) and related diseases. We analyzed SETBP1 in 1 130 patients with MPN and MDS/MPN overlap and found mutation frequencies of 3.8% and 9.4%, respectively. In particular, there was a high frequency of SETBP1 mutation in aCML (19/60; 31.7%) and MDS/MPN unclassifiable (MDS/MPN, U; 20/240; 9.3%). SETBP1 mutated (SETBP1mut) patients showed significantly higher white blood cell counts and lower platelet counts and hemoglobin levels than SETBP1 wild-type patients. Cytomorphologic evaluation revealed a more dysplastic phenotype in SETBP1mut cases as compared with wild-type cases. We confirm a significant association of SETBP1mut with -7 and isochromosome i(17)(q10). Moreover, SETBP1mut were strongly associated with ASXL1 and CBL mutations (P<0.001 for both) and were mutually exclusive of JAK2 and TET2 mutations. In conclusion, SETBP1mut add an important new diagnostic marker for MDS/MPN and in particular for aCML.
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Authors | M Meggendorfer, U Bacher, T Alpermann, C Haferlach, W Kern, C Gambacorti-Passerini, T Haferlach, S Schnittger |
Journal | Leukemia
(Leukemia)
Vol. 27
Issue 9
Pg. 1852-60
(Sep 2013)
ISSN: 1476-5551 [Electronic] England |
PMID | 23628959
(Publication Type: Journal Article)
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Chemical References |
- ASXL1 protein, human
- Carrier Proteins
- Nuclear Proteins
- Repressor Proteins
- SETBP1 protein, human
- Proto-Oncogene Proteins c-cbl
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Bone Marrow
(pathology)
- Carrier Proteins
(genetics)
- Chromosome Deletion
- Chromosomes, Human, Pair 7
- Female
- Humans
- Isochromosomes
- Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
(diagnosis, genetics, mortality)
- Male
- Middle Aged
- Mutation
- Mutation Rate
- Myelodysplastic Syndromes
(diagnosis, genetics, mortality)
- Myelodysplastic-Myeloproliferative Diseases
(diagnosis, genetics, mortality)
- Nuclear Proteins
(genetics)
- Proto-Oncogene Proteins c-cbl
(genetics)
- Repressor Proteins
(genetics)
- Young Adult
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