ABSTRACT
Inactivation of the non translocated TEL/ETV6 gene is commonly associated with translocation (12;21) of acute lymphoblastic leukemia (ALL). Translocations involving the short arm of chromosome 12 were analysed in two children with t(12;21) ALL. Fluorescence in situ hybridation studies showed that these associated translocations resulted in loss of TEL/ETV6. While hybridization with a YAC probe covering TEL/ETV6 was positive in one patient, analysis with cosmid probes covering the gene demonstrated that the gene was in fact deleted. It is concluded that deletions involving TEL/ETV6 can remain undetected by FISH using only YAC probes.
Subject(s)
Chromosomes, Human, Pair 12 , Chromosomes, Human, Pair 21 , DNA-Binding Proteins/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Repressor Proteins , Transcription Factors/genetics , Translocation, Genetic , Adolescent , Child, Preschool , Female , Humans , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/physiopathology , Proto-Oncogene Proteins c-ets , Recurrence , ETS Translocation Variant 6 ProteinABSTRACT
The types and incidences of secondary chromosomal abnormalities were analyzed in three subtypes of leukemia with recurrent abnormalities, translocations t(8;21), t(15;17), and inversion inv(16). The main types of clonal secondary abnormalities were similar to those described in the literature, loss of sex chromosome associated with t(8;21), trisomy 8 with t(15;17), and trisomies 8 or 22 with inv(16). On the whole, the incidence of clonal abnormalities was significantly higher in t(8;21) leukemia than in the two other subtypes. This difference was not related to a chromosomal instability peculiar to this leukemia subtype, because the incidence of nonclonal abnormalities was the same in the three types of leukemia studied. The significance of secondary clonal abnormalities remains speculative. A careful comparative analysis of structural rearrangements of the chromosomes usually involved in secondary abnormalities must be carried out as a first step to identify the key genes altered.
Subject(s)
Chromosome Aberrations , Leukemia, Myeloid/genetics , Acute Disease , Adult , Child , Chromosome Inversion , Chromosomes, Human, Pair 15 , Chromosomes, Human, Pair 16 , Chromosomes, Human, Pair 17 , Chromosomes, Human, Pair 21 , Chromosomes, Human, Pair 8 , Female , Humans , Male , Translocation, GeneticABSTRACT
Two patients with chromosome 16 inversion-associated translocation were studied with conventional cytogenetic and fluorescence in situ hybridization (FISH) techniques. The same chromosome 16 was involved in inversion and translocation in both patients. The chromosome translocation breakpoint was located within the heterochromatin of chromosome 16 but outside the alpha satellite domain in the t(10;16) of the first patient, whereas it was outside the heterochromatin area in the second case with t(1;16). These two types of rearrangements may be due to different mechanisms and illustrate the possible difficulties in recognizing the chromosome 16 inversion without FISH studies.
Subject(s)
Chromosome Inversion , Chromosomes, Human, Pair 16/genetics , Eosinophilia/genetics , Leukemia, Myelomonocytic, Acute/genetics , Translocation, Genetic/genetics , Adult , Bone Marrow Cells/metabolism , Bone Marrow Cells/pathology , Chromosome Banding , Chromosome Breakage/genetics , Chromosomes, Human, Pair 1/genetics , Chromosomes, Human, Pair 10/genetics , Eosinophilia/pathology , Female , Genetic Variation/genetics , Humans , In Situ Hybridization, Fluorescence , Karyotyping , Leukemia, Myelomonocytic, Acute/pathology , Male , Physical Chromosome MappingABSTRACT
The recurrent t(1;22)(p13;q13) translocation is exclusively associated with infant acute megakaryoblastic leukemia. We have identified the two genes involved in this translocation. Both genes possess related sequences in the Drosophila genome. The chromosome 22 gene (megakaryocytic acute leukemia, MAL) product is predicted to be involved in chromatin organization, and the chromosome 1 gene (one twenty-two, OTT) product is related to the Drosophila split-end (spen) family of proteins. Drosophila genetic experiments identified spen as involved in connecting the Raf and Hox pathways. Because almost all of the sequences and all of the identified domains of both OTT and MAL proteins are included in the predicted fusion protein, the OTT-MAL fusion could aberrantly modulate chromatin organization, Hox differentiation pathways, or extracellular signaling.