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Transmission of HLA-DP variants from parents to children with B-cell precursor acute lymphoblastic leukemia:

Malcolm Taylor1, Tracy L Bergemann, Adiba Hussain

  • 1Cancer Immunogenetics Group, School of Cancer and Enabling Sciences, University of Manchester, St. Mary's Hospital, Manchester, UK. gmtaylor@manchester.ac.uk

Human Immunology
|June 8, 2011
PubMed

Insights

Maternal HLA-DP variants were investigated for their role in childhood B-cell precursor acute lymphoblastic leukemia (BCP ALL). No association was found with DP1 or DP2, but infrequent DP11 and DP15 supertypes showed potential protective effects.

Area of Science:

  • Immunogenetics
  • Pediatric Oncology
  • Human Leukocyte Antigen (HLA) System

Background:

  • Childhood B-cell precursor acute lymphoblastic leukemia (BCP ALL) is thought to arise in utero and progress with infection exposure.
  • Previous studies suggested HLA-DP supertypes DP1 and DP2 influence BCP ALL susceptibility and protection.
  • Parental genetic effects could confound associations found in children, necessitating investigation of maternal influences.

Purpose of the Study:

  • To investigate the association between maternal Human Leukocyte Antigen (HLA)-DP variants and the risk of childhood B-cell precursor acute lymphoblastic leukemia (BCP ALL).
  • To explore potential parental genetic contributions to BCP ALL etiology.
  • To examine maternal transmission patterns of HLA-DP supertypes in BCP ALL cases.

Main Methods:

  • Log-linear models were applied to analyze family data, including triads (both parents and child) and dyads (one parent and child).
  • A cohort of 571 families with BCP ALL and 198 families with non-BCP leukemia were studied.
  • Maternal HLA-DP supertype frequencies were compared between BCP ALL cases and controls.

Main Results:

  • No significant association was observed between maternal DP1 or DP2 supertypes and BCP ALL.
  • Suggestive evidence indicated maternal undertransmission of infrequent supertypes DP11 and DP15 in BCP ALL families.
  • These findings point towards a potential protective role for DP11 and DP15 or transmission ratio distortion.

Conclusions:

  • Maternal HLA-DP1 and DP2 are not significantly associated with childhood BCP ALL risk.
  • Infrequent HLA-DP supertypes DP11 and DP15 may confer protection against BCP ALL or be subject to transmission distortion.
  • Further research is needed to confirm the role of DP11 and DP15 in BCP ALL pathogenesis.

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