Human leukocyte antigen-DR negative de novo acute myeloid leukemia with Philadelphia chromosome

Abstract

It is well known that human leukocyte antigen (HLA)-DR is present in the majority of acute myeloid leukemia (AML) [1, 2]. However, acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) usually lacks the HLA-DR expression as well as CD34 expression [2, 3]. Recently, such HLA-DR/CD34 phenotype has also been described in a subset of AML with cuplike nuclear invaginations (AML-cuplike) [4]. Cytogenetically or molecular genetically, AML-cuplike is characterized with normal karyotype and high frequency of FMS-like tyrosine kinase 3 (FLT3) gene internal tandem duplication (ITD) as well as nucleophosmin (NPM1) gene mutation [4, 5]. In this paper, we reported an extremely rare case of HLA-DR/CD34 AML, which was not categorized into either APL or AMLcuplike and showed Philadelphia chromosome (Ph) at diagnosis. A 64-year-old male was admitted to the hospital because of cellulitis of left leg in April 2008. He showed neither hepatosplenomegaly nor generalized lymph node swellings. There was no bleeding tendency. Laboratory findings were as follows: white blood cells 17.7 9 10/L, with 25% blasts and 20% basophils; hemoglobin, 14.0 g/dL; platelets, 129 9 10/L. Serum lactate dehydrogenase level and D-dimer was elevated to 386 IU/L and 50.2 lg/mL, respectively. Neutrophil alkaline phosphatase (NAP) score was within the normal range. Bone marrow showed hypercellularity with 39% blasts, 7% myelocytes, 4% metamyelocytes, 13% mature neutrophils, 1% eosinophils, 25% basophils, 8% erythroblasts and 3% lymphocytes. Morphologically, blasts were medium to large, and had round or sometimes slightly indented nuclei with dispersed chromatin. Fine azurophilic granules were sometimes found in their scant basophilic cytoplasm, but typical Auer-bodies were not detected (Fig. 1). They were cytochemically positive to myeloperoxidase (MPO) staining. Therefore, he was morphologically diagnosed as having AML-M2 according to the French–American–British (FAB) classification. There were no characteristic cuplike nuclear invaginations suggesting a diagnosis of AML-cuplike on either Wright–Giemsa or MPO staining [6]. Flow cytometric immunophenotyping using the CD45 gating method showed that leukemic blasts were CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD13, CD15, CD19, CD20, CD33, CD34, CD41, CD90, CD117 and HLA-DR, suggesting HLA-DR AML (Fig. 2). More than 85% of these cells also lacked the CD56 expression. Chromosomal analysis of bone marrow using the conventional G-banding method showed t(9;22)(q34;q11) in 14 of the 20 metaphases analyzed in addition to normal variance of inv(9)(p12q13) (Fig. 3). Fluorescence in situ hybridization (FISH) also showed BCR/ABL fusion signal in 92% of T. Inaba (&) N. Fujita Department of Infection Control and Laboratory Medicine, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan e-mail: inaba178@koto.kpu-m.ac.jp