Allelic loss on chromosome 4 (Lyr2/TLSR5) is associated with myeloid, B-lympho-myeloid, and lymphoid (B and T) mouse radiation-induced leukemias.
The CBA/H mouse model of radiation-induced acute myeloid leukemia (AML) was re-examined using molecular approaches. In addition to the typical promyelocytic AMLs, 34% were reclassified as early pre-B lympho-myeloid leukemias (L-ML) based on leukemic blood cell morphology, immunoglobulin heavy-chain gene re-arrangements (IgH(R)), or expression of both lymphoid (Vpre-B1 and Rag1) and myeloid (myeloperoxidase and lysozyme M) genes. Allelic loss on chromosome 4 was frequently detected in AMLs (53%) and L-MLs (more than 95%), and the preferential loss of the maternally transmitted allele suggests the locus may be imprinted. A minimally deleted region (MDR) maps to a 3.4-cM interval, which is frequently deleted in radiation-induced thymic lymphomas (TLSR5) and contains a recessive, maternally transmitted genetic locus (Lyr2) that confers resistance to spontaneous and radiation-induced pre-B and T cell lymphomas, suggesting they are one and the same. Thus, the Lyr2/TLSR5 locus is frequently implicated in myeloid, lymphoid (B and T), and mixed-lineage mouse leukemias and lymphomas. Epigenetic inactivation of one Lyr2/TLSR5 allele during normal mouse development suggests that only a single hit is required for its inactivation during leukemogenesis, and this may be a significant contributing factor to the efficiency of the leukemogenic process in the mouse.
Cleary
H
H
MRC Radiation and Genome Stability Unit, Chilton, Didcot, United Kingdom.
Boulton
E
E
Plumb
M
M
D000208:Acute Disease; D000483:Alleles; D000818:Animals; D002051:Burkitt Lymphoma / Q000209:etiology / Q000235:genetics / Q000473:pathology; D019070:Cell Lineage; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002874:Chromosome Mapping; D004273:DNA, Neoplasm / Q000235:genetics; D015322:Gene Rearrangement, B-Lymphocyte; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D005819:Genetic Markers; D018392:Genomic Imprinting; D007113:Immunity, Innate; D016130:Immunophenotyping; D007951:Leukemia, Myeloid / Q000209:etiology / Q000235:genetics / Q000473:pathology; D007953:Leukemia, Radiation-Induced / Q000145:classification / Q000235:genetics* / Q000473:pathology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000209:etiology / Q000235:genetics / Q000473:pathology; D019656:Loss of Heterozygosity; D008223:Lymphoma / Q000209:etiology / Q000235:genetics; D051379:Mice / Q000235:genetics*; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000235:genetics; D013154:Spleen / Q000473:pathology; D013953:Thymus Neoplasms / Q000209:etiology / Q000235:genetics
D004273:DNA, Neoplasm; D005819:Genetic Markers; D011947:Receptors, Antigen, B-Cell