Frequent but nonrandom expression of myeloid markers on de novo childhood acute lymphoblastic leukemia

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Abstract

The expression of the myeloid markers CD13, CD33, and CD15 in two hundred and eighty-three cases of de novo childhood acute lymphoblastic leukemia (ALL) is examined. The expression of at least one marker is a frequent event which is noted in 64% and 74% of B- and T-lineage ALL cases, respectively. Certain patterns of myeloid antigen expression can be recognized including: no expression of CD13, CD33, and CD15 in mature B-ALL, significantly higher levels of CD13 and CD33 and significantly lower levels of CD15 in TEL-AML1-positive B cell precursor ALL, no expression of CD13 and CD33 in E2A-PBX1-positive B cell precursor ALL cases and common T-ALL (double positive for CD4 and CD8), and no expression of CD13 in MLL-AF4-positive B cell precursor ALL cases. Although the numbers in some ALL subtypes are small, these patterns are consistent with nonrandom expression of myeloid markers in de novo childhood ALL.

Introduction

The expression of immunological markers of one hematopoietic lineage on the blasts of another lineage is a known feature of leukemia. Because of the frequency of this phenomenon in childhood leukemia, criteria for lineage determination have been suggested that limits the definition of true biphenotypic leukemia. Myeloid lineage commitment requires the expression of cytoplasmic myeloperoxidase, T-lineage commitment requires the expression of cytoplasmic CD3, and B-lineage commitment requires the expression of CD22 and CD19 or cytoplasmic 79a (Behm, 2006). The expression of markers of other lineages in cases that do not meet the definition of acute biphenotypic leukemia has been sometimes described as “aberrant”. In this paper, the expression of three myeloid markers, CD13, CD33, and CD15, is examined in de novo childhood acute lymphoblastic leukemia.

Section snippets

Flow cytometry protocol

Diagnostic four color flow cytometry includes the use of a panel of seven tubes in addition to isotype control as follows: FITC/PE/PerCP/APC (10/20/45/19 and 34/9/45/22 and 7/5/45/3 and 15/33/45/HLA-DR and 2/4/45/8 and 14/11b/45/13 and 61/41a/45/56). The expression of cytoplasmic antigens is performed by using two color analysis including CD45 (PerCP) and either CD79a (PE), TdT (FITC), MPO (FITC), CD3 (PE), or cIgM (FITC).

The following conjugated antibody clones were obtained from BD

Immunophenotypical and molecular subtypes of de novo childhood ALL

Two hundred and eighty-three cases of de novo childhood ALL (diagnosed between the years 2001 and 2006) are included. Two hundred and sixty cases (92%) are of B-lineage and 23 cases (8%) are of T-lineage. B-lineage cases include 255 cases (98%) of B cell precursor (BCP) ALL and 5 cases (2%) of mature B ALL.

Within BCP ALL cases, molecular subtypes are identified based on the expression of the most common fusion transcripts as determined by RT-PCR (Van Dongen et al., 1999) into sixty eight

Acknowledgment

The author wishes to acknowledge the excellent technical skills of past and present members of the Flow Cytometry and Molecular Haematopathology Laboratories at the Division of Haematopathology at the Hospital for Sick Children.

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