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Hematologic indices in individuals with pathogenic germline DICER1 variants
Lauren M Vasta1,2, Nicholas E Khan1,3, Cecilia P Higgs1
1Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD.
Blood Advances
|February 11, 2021
Summary
Germline DICER1 variants cause tumor predisposition. Hematologic abnormalities seen in mice were not observed in human DICER1 carriers, with limited evidence of secondary leukemia.
Area of Science:
- Genetics and Oncology
- Hematology
Background:
- Pathogenic germline variants in DICER1 are linked to a tumor predisposition disorder.
- Murine models with DICER1 loss show hematologic aberrations, including reduced blood cell counts and impaired maturation.
Purpose of the Study:
- To investigate if hematologic abnormalities observed in DICER1-deficient mice occur in humans with pathogenic germline DICER1 variants.
- To compare hematologic laboratory studies in DICER1 carriers and family controls.
Main Methods:
- A natural history study at the National Institutes of Health Clinical Center involving DICER1 carriers and family controls.
- Collection and comparison of routine clinical laboratory studies against normative values and between groups.
- Review of medical histories and query of the International Pleuropulmonary Blastoma/DICER1 Registry.
Main Results:
- No statistically significant differences in routine hematology laboratory studies were found between DICER1 carriers and family controls.
- None of the individuals in the NCI cohort developed myelodysplastic syndrome or leukemia.
- One DICER1 carrier in the registry developed secondary leukemia after pleuropulmonary blastoma treatment.
Conclusions:
- Limited evidence suggests hematologic abnormalities observed in murine DICER1 models do not consistently develop in human DICER1 carriers.
- Myelodysplastic syndrome was not observed; secondary leukemia is rare in this cohort.
- Hematologic index abnormalities should not be solely attributed to DICER1.
