Myeloperoxidase-positive acute leukemia with precursor B cell immunophenotype

Abstract

Is it always possible to make a complete diagnosis in leukemia? It is sometimes difficult to establish a clinical diagnosis in leukemia, especially without a concordance between morphology, immunophenotype, and genetic findings. Biphenotypic cases of leukemia [1], acute myeloid leukemia (AML) with lymphoid antigen [2], acute lymphoid leukemia (ALL) with myeloid antigen [3,4], and granular ALL [5] are typical examples of such diagnostic uncertainty. Acute leukemias of ambiguous lineage in the World Health Organization (WHO) 2008 classification constitute a small population of all cases of acute leukemia [6]. These cases are considered to be heterogeneous, and are therefore difficult to classify into particular groups. We report here a case in which the patient's leukemic blasts were positively stained for myeloperoxidase (MPO), and they were classified as morphologically apparent myeloid blasts, but their immunophenotype was of pre-B cell origin. The leukemia category 'MPOpositive acute leukemia with pre-B cell immunophenotype' has not been established, and therefore clinical features, differential diagnoses, and treatment have not been completely defined. In this report, we attempt to clarify the behavior of this type of leukemia, and analyze its sensitivity to antileukemia drugs in vitro, and in vivo by monitoring the clinical course of the disease.A 16-year-old boy presented with a 1.5-month history of sternal pain, appetite loss, general malaise, and low-grade fever. Splenomegaly and supraclavicular lymphadenopathy were detected. Laboratory examination revealed leukocytosis (white blood cell count 26.1 6 10 9 /L), thrombocytopenia (platelet count 73 6 10 9 /L), and elevated lactate dehydrogenase (LDH) activity (481 U/L). Large undifferentiated blasts, some of them with rough and large azurophilic granules, occupied 91.0% and 76.5% in the bone marrow and peripheral blood, respectively [ Figures 1(A) and 1(B)]. In the bone marrow, 3.6% of blasts were cytochemically stained for MPO [ Figure 1(C)], so we diagnosed the leukemia as AML (M1) according to the French-American-British (FAB) classification. Karyotype analysis showed 46,XY, and fluorescence in situ hybridization (FISH) showed no evidence of FLT3-internal tandem duplication (ITD), BCR-ABL, and MLL rearrangement. No chimeric fusion genes were identified with multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) examination. The immunophenotype was examined by flow cytometric (FCM) analysis, and bone marrow blasts were positively stained for cytoplasmic (cy) CD79a, cyCD22, CD19, CD10, CD34, and human leukocyte antigen-DR (HLA-DR): 92.9%, 92.3%, 84.2%, 95.0%, 92.1%, and 92.2%, respectively [ Figure 1(D)]. The patient's blasts were also stained for myeloid antigens CD33 and CD66c: 73.0% and 75.8%, respectively.Next, we confirmed that these blasts were sensitive to anti-leukemia drugs in vitro, especially how the sensitivity to anti-lymphoid agents was different from the sensitivity to anti-myeloid agents. First, we calculated the absolute blast c...