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International Journal of Hematology

, Volume 73, Issue 2, pp 206–212 | Cite as

Acute Myelogenous Leukemia WithPIG-A Gene Mutation Evolved from Aplastic Anemia—Paroxysmal Nocturnal Hemoglobinuria Syndrome

  • Hideo Tanaka
  • Nobutaka Imamura
  • Nobuo Oguma
  • Takahiro Shintani
  • Kimio Tanaka
  • Hideo Hyodo
  • Kenji Oda
  • Akiro Kimura
Case Report

Abstract

We report a patient with aplastic anemia (AA)—paroxysmal nocturnal hemoglobinuria (PNH) syndrome who developed acute myelogenous leukemia (AML). Flow cytometric analysis showed that the leukemic cells in the bone marrow lacked CD59 antigen on their surface and were positive for P-glycoprotein. Heteroduplex and single-strand conformation polymorphism analysis followed by sequencing of the leukemic cells in the bone marrow disclosed 1 frameshift-type mutation in exon 2 of the phosphatidylinositol glycan-class A (PIG-A) gene, which deductively produces truncated PIG-A protein. These findings provide direct evidence that the leukemic cells evolved from the affected PNH clone. Cytogenetic analysis in the bone marrow in each stage of AA-PNH, AML, and at relapse of AML showed normal, −7, and −7 plus −20, respectively, showing evidence of a clonal evolution. Because complete remission of AML was not achieved by intensive chemotherapies, allogeneic peripheral blood stem cell transplantation (PBSCT) from the patient’s HLA-matched sister was performed successfully with recovery of CD59 antigen on bone marrow hematopoietic cells; however, leukemia relapsed 4 months after PBSCT. Leukemia derived from PNH may be resistant to intensive chemotherapy, and a highly myeloablative regimen may be required for stem cell transplantation to eradicate the PNH-derived leukemia clone.

Key words

PNH Leukemia Chromosome PBSCT P-glycoprotein 

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Copyright information

© The Japanese Society of Hematology 2001

Authors and Affiliations

  • Hideo Tanaka
    • 1
  • Nobutaka Imamura
    • 1
  • Nobuo Oguma
    • 2
  • Takahiro Shintani
    • 2
  • Kimio Tanaka
    • 2
  • Hideo Hyodo
    • 1
  • Kenji Oda
    • 1
  • Akiro Kimura
    • 1
  1. 1.Department of Hematology and OncologyResearch Institute for Radiation Biology and Medicine, Hiroshima UniversityHiroshimaJapan
  2. 2.Department of Molecular CytogeneticsResearch Institute for Radiation Biology and Medicine, Hiroshima UniversityHiroshimaJapan

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