Families with multiple individuals with acute leukemia in their pedigrees

Area of Science:

• Genetics
• Hematology
• Oncology

Background:

• Familial acute leukemia presents unique inheritance patterns.
• Previous studies suggest autosomal dominant inheritance for familial acute leukemia.
• The role of sex chromosomes in leukemia inheritance requires further investigation.

Purpose of the Study:

• To analyze inheritance patterns in families with multiple cases of acute myeloid leukemia (AML) and B-cell acute lymphocytic leukemia (B-ALL).
• To investigate potential genetic factors, including those on the X chromosome, contributing to familial leukemia.
• To identify common features and inheritance patterns in multigenerational leukemia cases.

Main Methods:

• Collection and review of medical records from 41 families with multiple cases of de novo acute leukemia.
• Analysis of parent-child, grandparent-grandchild, and sibling relationships within affected families.
• Examination of disease concordance (AML-AML, B-ALL-B-ALL, AML-B-ALL) and sex concordance in affected pairs.

Main Results:

• Seventeen families showed parent-child acute leukemia pairs, with 15 being same-sex pairs.
• Nine grandparent-grandchild pairs with acute myeloid leukemia (AML-AML) were identified, six in same-sex pairs.
• Twenty families had multiple siblings with acute leukemia, including 16 pairs and 4 triples.
• Anticipation was observed in multigenerational pairs.
• While generally consistent with autosomal dominant inheritance, some patterns suggest a possible X chromosome gene involvement.

Conclusions:

• Familial acute leukemia exhibits complex inheritance patterns.
• The data support the hypothesis that an X chromosome gene, potentially in the pseudoautosomal region, may contribute to leukemia in some families.
• Further research is warranted to elucidate the genetic basis of familial acute leukemia, particularly the role of sex chromosomes.