Anticipation in familial leukemia

Marshall Horwitz, Ellen L Goode, Gail P. Jarvik

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

Anticipation refers to worsening severity or earlier age at onset with each generation for an inherited disease and primarily has been described for neurodegenerative illnesses resulting from expansion of trinucleotide repeats. We have tested for evidence of anticipation in familial leukemia. Of 49 affected individuals in nine families transmitting autosomal dominant acute myelogenous leukemia (AML), the mean age at onset is 57 years in the grandparental generation, 32 years in the parental generation, and 13 years in the youngest generation (P < .001). Of 21 parent-child pairs with AML, 19 show younger ages at onset in the child and demonstrate a mean decline in age at onset of 28 years (P < .001). Of 18 affected individuals from seven pedigrees with autosomal dominant chronic lymphocytic leukemia (CLL), the mean age at onset in the parental generation is 66 years versus 51 years in the youngest generation (P = .008). Of nine parent-child pairs with CLL, eight show younger ages at onset in the child and reveal a mean decline in age at onset of 21 years (P = .001). Inspection of rare pedigrees transmitting acute lymphocytic leukemia, chronic myelogenous leukemia, multiple types of leukemia, and lymphoma is also compatible with anticipation. Sampling bias is unlikely to explain these findings. This suggests that dynamic mutation of unstable DNA sequence repeats could be a common mechanism of inherited hematopoietic malignancy with implications for the role of somatic mutation in the more frequent sporadic cases. We speculate on three possible candidate genes for familial leukemia with anticipation: a locus on 21q22.1-22.2, CBL2 on 11q23.3, and CBFB or a nearby gene on 16q22.

Original languageEnglish (US)
Pages (from-to)990-998
Number of pages9
JournalAmerican Journal of Human Genetics
Volume59
Issue number5
StatePublished - 1996
Externally publishedYes

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Age of Onset
Leukemia
B-Cell Chronic Lymphocytic Leukemia
Pedigree
Acute Myeloid Leukemia
Unstable DNA Sequences
Trinucleotide Repeat Expansion
Mutation
Selection Bias
Hematologic Neoplasms
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Genes
Lymphoma

ASJC Scopus subject areas

  • Genetics

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Horwitz, M., Goode, E. L., & Jarvik, G. P. (1996). Anticipation in familial leukemia. American Journal of Human Genetics, 59(5), 990-998.

Anticipation in familial leukemia. / Horwitz, Marshall; Goode, Ellen L; Jarvik, Gail P.

In: American Journal of Human Genetics, Vol. 59, No. 5, 1996, p. 990-998.

Research output: Contribution to journalArticle

Horwitz, M, Goode, EL & Jarvik, GP 1996, 'Anticipation in familial leukemia', American Journal of Human Genetics, vol. 59, no. 5, pp. 990-998.
Horwitz, Marshall ; Goode, Ellen L ; Jarvik, Gail P. / Anticipation in familial leukemia. In: American Journal of Human Genetics. 1996 ; Vol. 59, No. 5. pp. 990-998.
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