Citation
Whitman, S P., et al. "Absence of the Wild-type Allele Predicts Poor Prognosis in Adult De Novo Acute Myeloid Leukemia With Normal Cytogenetics and the Internal Tandem Duplication of FLT3: a Cancer and Leukemia Group B Study." Cancer Research, vol. 61, no. 19, 2001, pp. 7233-9.
Whitman SP, Archer KJ, Feng L, et al. Absence of the wild-type allele predicts poor prognosis in adult de novo acute myeloid leukemia with normal cytogenetics and the internal tandem duplication of FLT3: a cancer and leukemia group B study. Cancer Res. 2001;61(19):7233-9.
Whitman, S. P., Archer, K. J., Feng, L., Baldus, C., Becknell, B., Carlson, B. D., Carroll, A. J., Mrózek, K., Vardiman, J. W., George, S. L., Kolitz, J. E., Larson, R. A., Bloomfield, C. D., & Caligiuri, M. A. (2001). Absence of the wild-type allele predicts poor prognosis in adult de novo acute myeloid leukemia with normal cytogenetics and the internal tandem duplication of FLT3: a cancer and leukemia group B study. Cancer Research, 61(19), 7233-9.
Whitman SP, et al. Absence of the Wild-type Allele Predicts Poor Prognosis in Adult De Novo Acute Myeloid Leukemia With Normal Cytogenetics and the Internal Tandem Duplication of FLT3: a Cancer and Leukemia Group B Study. Cancer Res. 2001 Oct 1;61(19):7233-9. PubMed PMID: 11585760.
TY - JOUR
T1 - Absence of the wild-type allele predicts poor prognosis in adult de novo acute myeloid leukemia with normal cytogenetics and the internal tandem duplication of FLT3: a cancer and leukemia group B study.
AU - Whitman,S P,
AU - Archer,K J,
AU - Feng,L,
AU - Baldus,C,
AU - Becknell,B,
AU - Carlson,B D,
AU - Carroll,A J,
AU - Mrózek,K,
AU - Vardiman,J W,
AU - George,S L,
AU - Kolitz,J E,
AU - Larson,R A,
AU - Bloomfield,C D,
AU - Caligiuri,M A,
PY - 2001/10/5/pubmed
PY - 2001/10/19/medline
PY - 2001/10/5/entrez
SP - 7233
EP - 9
JF - Cancer research
JO - Cancer Res
VL - 61
IS - 19
N2 - The FLT3 gene is mutated by an internal tandem duplication (ITD) in 20-25% of adults with acute myeloid leukemia (AML). We studied 82 adults <60 years of age with primary AML and normal cytogenetics, who received uniform high-dose therapy and found FLT3 ITD in 23 (28%) patients. When the 23 FLT3 ITD+ cases were compared with the 59 cases with wild-type (WT) FLT3, disease-free survival (DFS) was inferior (P = 0.03), yet overall survival (OS) was not different (P = 0.14). However, 8 (35%) of 23 FLT3 ITD/+ cases also lacked a FLT3 WT allele (FLT3(ITD-R)) as determined by PCR and loss of heterozygosity. Thus, three genotypic groups were identified: normal FLT3(WT/WT), heterozygous FLT3(ITD/WT), and hemizygous FLT3(ITD/-). DFS and OS were significantly inferior for patients with FLT3(ITD/-) (P = 0.0017 and P = 0.0014, respectively). Although DFS and OS for FLT3(WT/WT) and FLT3(ITD/WT) groups did not differ (P = 0.32 and P = 0.98, respectively), OS of the FLT3(ITD/-) group was worse than the FLT3(WT/WT) (P = 0.0005) and FLT3(ITD/WT) (P = 0.008) groups. We propose a model in which FLT3(ITD/-) represents a dominant positive, gain-of-function mutation providing AML cells with a greater growth advantage compared with cells having the FLT3(WT/WT) or FLT3(ITD/WT) genotypes. In conclusion, we have identified the FLT3(ITD/-) genotype as an adverse prognostic factor in de novo AML with normal cytogenetics. A poor prognosis of the relatively young FLT3(ITD/-) adults (median age, 37 years), despite treatment with current dose-intensive regimens, suggests that new treatment modalities, such as therapy with a FLT3 tyrosine kinase inhibitor, are clearly needed for this group of patients.
SN - 0008-5472
UR - https://www.unboundmedicine.com/medline/citation/11585760/Absence_of_the_wild_type_allele_predicts_poor_prognosis_in_adult_de_novo_acute_myeloid_leukemia_with_normal_cytogenetics_and_the_internal_tandem_duplication_of_FLT3:_a_cancer_and_leukemia_group_B_study_
L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=11585760
DB - PRIME
DP - Unbound Medicine
ER -
