ABSTRACT
Ninety-two Israeli children with acute lymphoblastic leukemia (ALL) (67 B-lineage and 25 T-lineage) were analyzed for the immunological antigen receptor gene configuration. Thirty-nine of the patients (27 B-lineage and 12 T-lineage) relapsed. The incidence of the identified rearrangements within the immunoglobulin heavy chain (IgH) and T-cell receptor (TCR)beta, gamma and delta genes, at diagnosis, was in accordance with previous studies from other countries. Furthermore, the clinical relevance of bi/oligoclonal status, at diagnosis, and clonal selection was determined in this long-term follow-up study (median 112 months). A similar relapse rate was observed among the B-lineage patients with bi/oligoclonal and monoclonal patterns indicated by IgH gene rearrangement. Based on our results, we suggest that bi/oligoclonality has no prognostic significance (P=0.8533). Clonal variations between diagnosis and subsequent relapses were detected in 60% (12/20) of the patients; 64% (7/11) B-lineage and 55% (5/9) T-lineage. Clonal selection significantly correlated with shorter duration of remission and earlier recurrence (P=0.0025).
Subject(s)
Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Adolescent , B-Lymphocytes/immunology , B-Lymphocytes/physiology , Blotting, Southern , Cell Lineage/genetics , Cell Lineage/immunology , Child , Child, Preschool , Clone Cells/immunology , Clone Cells/physiology , DNA/analysis , Female , Gene Rearrangement, B-Lymphocyte, Heavy Chain/genetics , Gene Rearrangement, T-Lymphocyte/genetics , Humans , Immunophenotyping , Incidence , Infant , Israel/epidemiology , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology , Prognosis , Recurrence , T-Lymphocytes/immunology , T-Lymphocytes/physiology , Time FactorsABSTRACT
Recent studies have established the presence of human T cell leukemia/lymphoma virus type I (HTLV-I) in Israel. The entire nucleotide sequence of HTLV-I virus from a previously described HE isolate of a Mashadi Jewish Iranian patient was determined. To further characterize the LTR and env genes from the HTLV-I isolate we employed polymerase chain reaction amplification with subsequent cloning and sequencing of the amplified products on both strands. Sequence analyses of amplified LTR regions of this variant showed marked nucleotide homology of 98% compared to Japanese isolates, while African and Indo-Malay (Papua, New Guinea) and Solomon Island isolates showed more divergence with sequence homology of 95% and 91%. Higher homology of 98-99% was conserved in the amplified HTLV-env gene. In this respect the Iranian isolate was most similar to the African and Japanese isolate and divergent from the Melanesian HTLV-I variant, supporting the theory that HTLV-I may have originated in Africa and reached the Far East by overland trade routes.
Subject(s)
DNA, Viral , Human T-lymphotropic virus 1/genetics , Africa , Base Sequence , Cell Line , Genes, env , Genome, Viral , Humans , Israel , Japan , Melanesia , Molecular Sequence Data , Polymerase Chain Reaction , Repetitive Sequences, Nucleic AcidABSTRACT
To define the extent of human T-cell leukaemia virus (HTLV-I) infection among a group of Jewish immigrants to Israel with an increased frequency of adult T-cell leukaemia, various serological and molecular screening methods, including enzyme-linked immunosorbent assay (ELISA) for anti-HTLV-I, ELISA for antibody to recombinant HTLV-I p40tax protein, and molecular detection of infection by polymerase chain reaction (PCR) amplification of HTLV-I proviral DNA from peripheral blood mononuclear cell DNA, were used. By HTLV-I ELISA the overall rate of infection was 12% (24 of 208) among immigrants from Khurusan, northeastern Iran; no HTLV-I carriers were detected among 111 unselected Jewish immigrants from other parts of Iran. There was unexplained clustering of HTLV-I infection within a cohort of 32 elderly women of similar geographic origin in a home for old people--14 were seropositive by ELISA and 19 of 29 were positive by PCR. The findings in this newly identified high-risk population suggest that in addition to ELISA, other screening techniques may be required to detect all carriers in high-risk populations.
