CD19 negative precursor B acute lymphoblastic leukemia (B-ALL)-Immunophenotypic challenges in diagnosis and monitoring: A study of three cases

Cytometry B Clin Cytom. 2017 Jul;92(4):315-318. doi: 10.1002/cyto.b.21373. Epub 2016 Jun 8.

Abstract

Background: CD19 is a B-cell specific marker, expressed on all stages of B-lymphocytes including plasma cells. It is widely used in the flow cytometric immunophenotyping (FCI) of B-cell and plasma cell malignancies. The analysis approach of FCI for the diagnosis and monitoring of B-cell acute lymphoblastic leukemia (B-ALL) is totally based on the CD19-based primary gating strategy and it would be challenging to study B-ALL without CD19 expression. Since CD19 negative B-ALL are extremely rare, we report three cases of B-ALL with negative expression of CD19 and discussed its implication in the diagnosis, residual disease monitoring and future targeted therapy.

Methods: Peripheral blood (PB) and bone marrow (BM) samples from three cases suspicious of acute leukemia were studied for morphology, cytochemistry, immunophenotyping and cytogenetics. FCI was performed using a comprehensive six to eight-color multiparametric assay. The cytogenetic studies for standard recurrent genetic translocations were performed by FISH & Karyotyping.

Results: The three cases studied were diagnosed as B-ALL based on the expression of CD10, CD20, CD22, CD34, and CD79a by leukemic blasts. CD19 was studied using two different clones (i.e. J3-119 & HIB-19) and found to be severely down regulated in all three cases. There were no significant differentiating features in morphology. Cytogenetic studies were negative for recurrent translocations.

Conclusion: We report three cases of extremely rare CD19 negative B-ALL. Lack of awareness of negative CD19 expression in B-ALL can leads to incorrect immunophenotypic diagnosis and monitoring of B-ALL, especially in laboratories using limited markers. © 2016 International Clinical Cytometry Society.

Keywords: B-cell acute lymphoblastic leukemia; CD19; Flow cytometric immunophenotyping (FCI).

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Antibodies / chemistry
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Antigens, CD19 / genetics*
  • Antigens, CD19 / immunology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology*
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / pathology*
  • Child
  • Child, Preschool
  • Down-Regulation
  • Female
  • Flow Cytometry
  • Gene Expression
  • Humans
  • Immunophenotyping / methods*
  • Karyotyping
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / diagnosis*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology

Substances

  • Antibodies
  • Antigens, CD
  • Antigens, CD19
  • CD19 molecule, human