α, β and γ T-cell receptor genes: rearrangements correlate with haematological phenotype in T cell leukaemias

Abstract

We have studied the arrangement of the alpha, beta and gamma T cell receptor (TCR) genes in 27 patients with T cell lymphoproliferative disorders. Nine patients had acute lymphoblastic leukaemia (T-ALL), nine patients had prolymphocytic leukaemia (PLL), six patients presented with a T-CLL/T-lymphocytosis syndrome, two patients had Sezary syndrome (SS) and one patient had HTLV-I positive T-cell leukaemia/lymphoma (ATLL). alpha TCR gene rearrangement could be demonstrated by the use of three available probes in only one case. By contrast, both beta and gamma TCR gene rearrangement could be demonstrated by Southern blot analysis of DNA samples digested with appropriate restriction enzymes in the majority of cases. In general, when rearrangements were present they involved both alleles. The proportion of rearranged chromosomes was lower in T-ALL than in other forms of T-cell leukaemia and it was lower in cases with the CD4-/CD8+ phenotype than in those with a CD4+/CD8- phenotype. In three out of 34 cases of B-cell leukaemia the TCR beta-gene but not the TCR gamma-gene was rearranged, just as in two out of 26 cases of T-cell leukaemia the immunoglobulin (Ig) heavy chain but not the light chain genes were rearranged. These data suggest that development of the machinery required for gene rearrangement may precede commitment to B or T cell lineage. The use of this technique is especially useful for the classification of cases of ALL in which the cells are negative with respect to most current phenotypic markers and in cases of T cell lymphocytosis in which the finding of a gene rearrangement identifies a monoclonal cell population.

Relationship between Chromosomal Breakpoint and Molecular Rearrangement of T-Cell Antigen Receptors in Adult T-Cell Leukaemia

“…It is well known that TCR-[5 rearrangement can be demonstrat ed in the majority of cases with T-cell malignancies [26,27] including ATL [28]. However, Matsuoka et al [28] concluded that the nucleotide sequence analyses of Vp genes did not support the receptor-mediated leukaemogenesis theory for ATL.…”

Diverse point mutations in the human glucose-6-phosphate dehydrogenase gene cause enzyme deficiency and mild or severe hemolytic anemia.

“…DNA was prepared from whole blood or Epstein-Barr virus-transformed lymphocytes (14). Phage A genomic libraries were constructed from this DNA after it had been digested with HindIll or EcoRI and size-fractionated on 0.5% agarose gels or 10-40% sucrose gradients.…”

Extramedullary blast crisis in chronic myelogenous leukemia. Demonstration of t-cell lineage and philadelphia chromosome in a paraspinal tumor

“…Hepatosplenomegaly was noticed on physical examination. Laboratory data showed a hemoglobin of 10.8 g/dl, hematocrit 35.8570, and leukocyte count 178 X 109/1 with the differential typical of chronic myelogenous leukemia. A nuclear liver/spleen scan revealed splenomegaly and a probable splenic infarct.…”