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Two consecutive immunophenotypic switches in a child with immunogenotypically stable acute leukaemia
M Bierings1, T Szczepański, E R van Wering
1Department of Haematology and Stem Cell Transplantation, University Medical Centre, Het Wilhelmina Kinderziekenhuis, Utrecht, The Netherlands. m.bierings@wkz.azu.nl
British Journal of Haematology
|June 19, 2001
Summary
This study details a rare case of precursor B-acute lymphoblastic leukemia (ALL) that rapidly transformed into acute myeloid leukemia (AML) in a child, highlighting a significant phenotypic shift in leukemia. The genotypically stable leukemia demonstrated a remarkable ability to change its cell type, suggesting a versatile progenitor clone.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Precursor B-acute lymphoblastic leukemia (ALL) is a common childhood malignancy.
- Phenotypic shifts in leukemia, while rare, can complicate treatment and prognosis.
- Understanding the molecular basis of these shifts is crucial for developing targeted therapies.
Observation:
- A 12-year-old girl diagnosed with CD33+ precursor B-acute lymphoblastic leukemia (ALL) showed initial response to treatment.
- Within two weeks, she developed acute myeloid leukemia (AML) with M5b morphology and a myeloid immunophenotype.
- After AML treatment and remission, she relapsed with an undifferentiated blast morphology and a precursor B immunophenotype.
Findings:
- Molecular analysis revealed clonal gene rearrangements (IGH, IGK, TCRD) present throughout all disease phases, indicating a single underlying leukemia.
- The leukemia underwent a rapid phenotypic shift from B-lymphoid to myeloid and back to an undifferentiated state.
- Genotypic stability with rapid phenotypic plasticity suggests an origin in a highly versatile hematopoietic progenitor.
Implications:
- This case underscores the potential for significant phenotypic plasticity in leukemia, challenging conventional treatment paradigms.
- The findings suggest that early oncogenic events in multipotent hematopoietic progenitors may lead to diverse leukemic phenotypes.
- Further research into the mechanisms driving these rapid phenotypic shifts could reveal novel therapeutic targets for relapsed or refractory leukemia.