Aberrant Expression of CD7 in Myeloblasts Is Highly Associated With De Novo Acute Myeloid Leukemias With FLT3/ITD Mutation

Division of Pathology, City of Hope National Medical Center, Duarte, CA 91010, USA.
American Journal of Clinical Pathology (Impact Factor: 2.51). 05/2008; 129(4):624-9. DOI: 10.1309/NRTX9AKXHR5JBT93
Source: PubMed


Acute myeloid leukemia (AML) with normal cytogenetics represents approximately 40% to 50% of de novo AML. This heterogeneous AML subgroup constitutes the single largest cytogenetic group with an intermediate prognosis. Previous studies have suggested that the Fms-like tyrosine kinase-3 internal tandem duplication (FLT3/ITD) mutation-positive de novo AML may represent a distinctive subgroup of AML. We analyzed the clinical and pathologic features of 15 cases of de novo AML with normal cytogenetics and with the FLT3/ITD mutation. In comparison with patients with AML without the FLT3/ITD mutation, patients with FLT3/ITD+ AML are relatively younger, more often have marked peripheral leukocytosis with a higher number of circulating blasts at initial examination, more often have minimal differentiation morphologic features, more frequently have abnormal CD7 coexpression, and have poorer outcome. Close association of aberrant CD7 expression and FLT3/ITD mutation in the myeloblasts of FLT3/ITD+ AML suggests that FLT3/ITD- mediated leukemic transformation occurs in the more early stage of myeloid progenitor cells.

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    • "Though FLT3/ITD patients did not display a unique immunophenotype, a significant association of FLT3/ITD mutation with aberrant expression of CD7 was found (P = 0.04). An earlier study by us and Rausei-Mills et al., 2008 has also shown the association of coexpression of CD7 antigen with FLT3/ITD mutation [10, 28]. "
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    ABSTRACT: Background: Mutations in NPM1 and FLT3 genes represent the most frequent genetic alterations and important diagnostic and prognostic indicators in patients with acute myeloid leukemia (AML). Objective: We investigated the prevalence and clinical characteristics of NPM1 and FLT3 mutations in 161 patients of de novo AML including adults and children. Results: NPM1 mutation was found in 21% and FLT3 mutation in 25% of the AML patients. Thirteen (8%) samples were positive for both NPM1 and FLT3/ITD mutations. Adult patients had significantly higher frequency of NPM1 mutation than children (25.8% versus 8.8%; P = 0.02). Further, NPM1 mutation was found to be more frequent in patients above 45 years of age (P = 0.02). NPM1 mutation was significantly associated with higher platelet count (P = 0.05) and absence of hepatosplenomegaly (P = 0.01), while FLT3/ITD mutation was associated with higher white blood count (P = 0.01). Immunophenotypically, NPM1 mutation was associated with the lack of CD34 (P < 0.001) and HLD-DR expression (P < 0.001), while FLT3/ITD mutation was positively associated with the expression of CD7 (P = 0.04). No correlation was found between NPM1 mutation and fusion gene. Interestingly, FLT3/ITD mutation was found to be inversely associated with AML/ETO fusion gene (P = 0.04). Conclusions: The results suggest that distinct clinical and immunophenotypic characteristics of NPM1 and FLT3/ITD mutations present further insight into the molecular mechanism of leukemogenesis.
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    ABSTRACT: To analyze the spectrum of various types and subtypes of acute leukemia. Two thousand five hundred and eleven consecutive new referral cases of acute leukemia (AL) were evaluated based on WHO classification. It included 1,471 cases (58%) of acute lymphoblastic leukemia (ALL), 964 cases (38%) of acute myeloid leukemia (AML), 45 cases (1.8%) of chronic myelogenous leukemia in blast crisis (CMLBC), 37 cases (1.5%) of biphenotypic acute leukemia (BAL), 1 case of Triphenotypic AL, and 2 cases of acute undifferentiated leukemia (AUL). Common subtypes of ALL were B-cell ALL (76%), which comprised of intermediate stage/CALLA positive (73%), early precursor/proBALL (3%). T-cell ALL constituted 24% (351 cases) of ALL. Common subtypes of AML included AMLM2 (27%), AMLM5 (15%), AMLM0 (12%), AMLM1 (12%), APML (11%), and AML t(8;21) (9%). CMLBC was commonly of myeloid blast crisis subtype (40 cases). B-cell ALL was the commonest subtype in children and AML in adults. Overall incidence of AML in adults was low (53% only). CD13 was most sensitive and CD117 most specific for determining myeloid lineage. A minimal primary panel of nine antibodies consisting of three myeloid markers (CD13, CD33, and CD117), B-cell lymphoid marker (CD19), T-cell marker (CD7), with CD45, CD10, CD34, and HLADR could assign lineage to 92% of AL. Cytogenetics findings lead to a change in the diagnostic subtype of myeloid malignancy in 38 (1.5%) cases.
    Cytometry Part B Clinical Cytometry 05/2009; 76(3):199-205. DOI:10.1002/cyto.b.20451 · 2.40 Impact Factor
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