Related Experiment Video
Updated: Aug 14, 2026
Flow Cytometry to Estimate Leukemia Stem Cells in Primary Acute Myeloid Leukemia and in Patient-derived-xenografts, at Diagnosis and Follow Up
Published on: March 26, 2018
Mixed acute leukemia with genotypic lineage switch: a case report
S Ciolli1, F Leoni, R Caporale
1Division at Hematology, University of Florence, Italy.
Insights
This study details a rare acute myeloid leukemia case that switched to a lymphoid phenotype, then back to myeloid. Genomic analysis revealed a consistent TCR delta gene rearrangement, suggesting an early pathogenetic event.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- Leukemias typically present with distinct morphologic and phenotypic characteristics.
- Mixed-phenotype leukemias, while rare, present diagnostic and therapeutic challenges.
- Understanding phenotypic plasticity is crucial for leukemia management.
Observation:
- A case of acute myeloid leukemia (AML) initially co-expressed B-lymphoid markers.
- Upon relapse, the leukemia underwent a complete phenotypic and genotypic switch to a lymphoid form.
- Further relapse saw the re-emergence of myeloid features, retaining specific genomic rearrangements.
Findings:
- Immunoglobulin (Ig) H and T-cell receptor (TCR) gene analysis revealed germline configuration at diagnosis, with a TCR delta deletion.
- Monoclonal rearrangements of IgH, TCR tau, and TCR delta were detected at first relapse.
- Consistent TCR delta gene configuration across disease phases suggests an early pathogenetic event, deeming a second malignancy unlikely.
Implications:
- Phenotypic evolution in leukemia can be influenced by chemotherapy.
- Genomic alterations, particularly TCR delta gene configuration, can serve as lineage-independent markers.
- This case highlights the complex interplay between genotype, phenotype, and treatment response in leukemia.
Abstract:
Morphologically well classifiable leukemias can reveal a mixed phenotype. A case of acute myeloid leukemia (CD13, CD33, CD14, CD11b) which at presentation showed a co-expression of B-lymphoid markers (CD19, CD10, CD20), at the time of the first relapse revealed a morphologic, phenotypic and genotypic switch of the blasts to a purely lymphoid form. Analysis of the immunoglobulin (Ig) H chain locus and of the T-cell receptor (TCR) genes showed at diagnosis a germline configuration of the IgH, TCR beta and tau genes, and a deletion of the TCR delta gene at the second chromosome. At relapse, monoclonal rearrangements of the IgH, TCR tau, and TCR delta were detected. At a subsequent relapse, the blasts re-expressed myeloid morphologic features and myeloid-associated antigens, while they retained the same rearranged configuration of the IgH and TCR beta and delta genes. The TCR delta gene configuration, which links each phase of the disease, may represent an early pathogenetic event and makes the emergence of a second malignancy unlikely. Each phenotypic change occurred after anti-myeloid and anti-lymphoid oriented chemotherapy. The close correlation between the progressive acquisition of different phenotypes and the switch at the genomic level represent the peculiar features of this unusual case.
