FLT3 and NPM1 mutations in myelodysplastic syndromes: Frequency and potential value for predicting progression to acute myeloid leukemia

American Journal of Clinical Pathology

Volumn 135, Issue 1, 2011, Pages 62-69

  Bains, Ashish ^a,b   Luthra, Rajyalakshmi ^a   Medeiros, L Jeffrey ^a   Zuo, Zhuang ^a  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b UNIVERSITY OF OKLAHOMA COLLEGE OF MEDICINE   (United States)

Author keywords

FLT3; FMS like tyrosine kinase; Mutation; Myelodysplastic syndromes; NPM1; Nucleophosmin

Indexed keywords

FLT3 LIGAND; NUCLEOPHOSMIN;

ACUTE GRANULOCYTIC LEUKEMIA; ADOLESCENT; ADULT; AGED; ARTICLE; BONE MARROW CELL; CELL COUNT; COHORT ANALYSIS; CYTOGENETICS; DISEASE COURSE; FEMALE; GENE MUTATION; GENETIC ASSOCIATION; GENETIC RISK; GROUPS BY AGE; HUMAN; KARYOTYPE; MAJOR CLINICAL STUDY; MALE; MUTATION RATE; MUTATIONAL ANALYSIS; MYELODYSPLASTIC SYNDROME; PANCYTOPENIA; PREDICTOR VARIABLE; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; RISK ASSESSMENT;

ADOLESCENT; ADULT; AGED; AGED, 80 AND OVER; BONE MARROW CELLS; CHROMOSOME ABERRATIONS; DISEASE PROGRESSION; FEMALE; FMS-LIKE TYROSINE KINASE 3; GENETIC PREDISPOSITION TO DISEASE; HUMANS; LEUKEMIA, MYELOID, ACUTE; MALE; MIDDLE AGED; MUTATION; MYELODYSPLASTIC SYNDROMES; NUCLEAR PROTEINS; PROGNOSIS; RETROSPECTIVE STUDIES; SURVIVAL RATE; TEXAS; YOUNG ADULT;

EID: 79251500335     PISSN: 00029173     EISSN: 19437722     Source Type: Journal    
DOI: 10.1309/AJCPEI9XU8PYBCIO     Document Type: Article

References (23)

1. Olney HJ, Le Beau MM. Evaluation of recurring cytogenetic abnormalities in the treatment of myelodysplastic syndromes. Leuk Res. 2007;4:427-434.
2. Drexler HG. Expression of FLT3 receptor and response to FLT3 ligand by leukemic cells. Leukemia. 1996;4:588-599. (Pubitemid 26144436)
3. Kottaridis PD, Gale RE, Frew ME, et al. The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood. 2001;6:1752-1759.
4. Bacher U, Haferlach C, Kern W, et al. Prognostic relevance of FLT3-TKD mutations in AML: the combination matters: an analysis of 3082 patients. Blood. 2008;5:2527-2537.
5. Schneider F, Hoster E, Unterhalt M, et al. NPM1 but not FLT3-ITD mutations predict early blast cell clearance and CR rate in patients with normal karyotype AML (NK-AML) or high-risk myelodysplastic syndrome (MDS). Blood. 2009;21:5250-5253.
6. Horiike S, Yokota S, Nakao M, et al. Tandem duplications of the FLT3 receptor gene are associated with leukemic transformation of myelodysplasia. Leukemia. 1997;9:1442-1446. (Pubitemid 27404382)
7. Pinheiro RF, de Sa Moreira E, Silva MR, et al. FLT3 internal tandem duplication during myelodysplastic syndrome follow-up: a marker of transformation to acute myeloid leukemia. Cancer Genet Cytogenet. 2008;2:89-93. (Pubitemid 351707708)
8. Bacher U, Haferlach T, Kern W, et al. A comparative study of molecular mutations in 381 patients with myelodysplastic syndrome and in 4130 patients with acute myeloid leukemia. Haematologica. 2007;6:744-752. (Pubitemid 350155299)
9. Schnittger S, Schoch C, Kern W, et al. Nucleophosmin gene mutations are predictors of favorable prognosis in acute myelogenous leukemia with a normal karyotype. Blood. 2005;12:3733-3739.
10. Szankasi P, Jama M, Bahler DW. A new DNA-based test for detection of nucleophosmin exon 12 mutations by capillary electrophoresis. J Mol Diagn. 2008;3:236-241.
11. Falini B, Mecucci C, Tiacci E, et al. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med. 2005;3:254-266. (Pubitemid 40110814)
12. Grisendi S, Pandolfi PP. NPM mutations in acute myelogenous leukemia. N Engl J Med. 2005;3:291-292.
13. Zhang Y, Zhang M, Yang L, et al. NPM1 mutations in myelodysplastic syndromes and acute myeloid leukemia with normal karyotype. Leuk Res. 2007;1:109-111.
14. Brunning RD, Orazi A, Germing U, et al. Myelodysplastic syndromes/neoplasms, overview. In: Swerdlow SH, Campo E, Harris NL, et al, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon, France: IARC Press; 2008:88-93.
15. Gustafson SA, Lin P, Chen SS, et al. Therapy-related acute myeloid leukemia with t(8;21)(q22;q22) shares many features with de novo acute myeloid leukemia with t(8;21)(q22;q22) but does not have a favorable outcome. Am J Clin Pathol. 2009;131:647-655.
16. Chen W, Jones D, Medeiros LJ, et al. Acute myeloid leukaemia with FLT3 gene mutations of both internal tandem duplication and point mutation type. Br J Haematol. 2005;5:726-728.
17. Konoplev S, Huang X, Drabkin HA, et al. Cytoplasmic localization of nucleophosmin in bone marrow blasts of acute myeloid leukemia patients is not completely concordant with NPM1 mutation and is not predictive of prognosis. Cancer. 2009;115:4737-4744.
18. Zuo Z, Chen SS, Chandra PK, et al. Application of COLD-PCR for improved detection of KRAS mutations in clinical samples. Mod Pathol. 2009;8:1023-1031.
19. Sportoletti P, Grisendi S, Majid SM, et al. Npm1 is a haploinsufficient suppressor of myeloid and lymphoid malignancies in the mouse. Blood. 2008;7:3859-3862.
20. Dohner K, Schlenk RF, Habdank M, et al. Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics: interaction with other gene mutations. Blood. 2005;12:3740-3746.
21. Kelly LM, Gilliland DG. Genetics of myeloid leukemias. Annu Rev Genomics Hum Genet. 2002;3:179-198.
22. Bernasconi P. Molecular pathways in myelodysplastic syndromes and acute myeloid leukemia: relationships and distinctions: a review. Br J Haematol. 2008;5:695-708.
23. Shih LY, Huang CF, Wang PN, et al. Acquisition of FLT3 or N-ras mutations is frequently associated with progression of myelodysplastic syndrome to acute myeloid leukemia. Leukemia. 2004;3:466-475.