Minimal residual disease levels in bone marrow and peripheral blood are comparable in children with T cell acute lymphoblastic leukemia (ALL), but not in precursor-B-ALL.
(1/266)
Sensitive and quantitative detection of minimal residual disease (MRD) in bone marrow (BM) samples of children with acute lymphoblastic leukemia (ALL) is essential for evaluation of early treatment response. In this study, we evaluated whether the traumatic BM samplings can be replaced by peripheral blood (PB) samplings. MRD levels were analyzed in follow-up samples of 62 children with precursor-B-ALL (532 paired BM-PB samples) and 22 children with T-ALL (149 paired BM-PB samples) using real-time quantitative PCR (RQ-PCR) analysis of immunoglobulin and T cell receptor gene rearrangements with sensitivities of 10(-3) to 10(-5) (one ALL cell in 10(3) to 10(5) normal cells). In 14 of the 22 T-ALL patients, detectable MRD levels were found in 67 paired BM-PB samples: in 47 pairs MRD was detected both in BM and PB, whereas in the remaining pairs very low MRD levels were detected in BM (n = 11) or PB (n = 9) only. The MRD levels in the paired BM-PB samples were very comparable and strongly correlated (r(s) = 0.849). Comparable results were obtained earlier by immunophenotyping in 26 T-ALL patients (321 paired BM-PB samples), which also showed a strong correlation between MRD levels in paired BM and PB samples (r(s) = 0.822). In 39 of the 62 precursor-B-ALL patients, MRD was detected in 107 BM-PB pairs: in 48 pairs MRD was detected in both BM and PB, in 47 pairs MRD was solely detected in BM (at variable levels), and in 12 pairs only the PB sample was MRD-positive at very low levels (+info)
No genetic evidence for involvement of Deltaretroviruses in adult patients with precursor and mature T-cell neoplasms.
(2/266)
BACKGROUND: The Deltaretrovirus genus comprises viruses that infect humans (HTLV), various simian species (STLV) and cattle (BLV). HTLV-I is the main causative agent in adult T-cell leukemia in endemic areas and some of the simian T-cell lymphotropic viruses have been implicated in the induction of malignant lymphomas in their hosts. BLV causes enzootic bovine leukosis in infected cattle or sheep. During the past few years several new Deltaretrovirus isolates have been described in various primate species. Two new HTLV-like viruses in humans have recently been identified and provisionally termed HTLV-III and HTLV-IV. In order to identify a broad spectrum of Deltaretroviruses by a single PCR approach we have established a novel consensus PCR based on nucleotide sequence data obtained from 42 complete virus isolates (HTLV-I/-II, STLV-I/-II/-III, BLV). The primer sequences were based on highly interspecies-conserved virus genome regions. We used this PCR to detect Deltaretroviruses in samples from adult patients with a variety of rare T-cell neoplasms in Germany. RESULTS: The sensitivity of the consensus PCR was at least between 10-2 and 10-3 with 100% specificity as demonstrated by serial dilutions of cell lines infected with either HTLV-I, HTLV-II or BLV. Fifty acute T-cell lymphoblastic leukemia (T-ALL) samples and 33 samples from patients with various rare mature T-cell neoplasms (T-PLL, Sezary syndrome and other T-NHL) were subsequently investigated. There were no cases with HTLV-I, HTLV-II or any other Deltaretroviruses. CONCLUSION: The results rule out a significant involvement of HTLV-I or HTLV-II in these disease entities and show that other related Deltaretroviruses are not likely to be involved. The newly established Deltaretrovirus PCR may be a useful tool for identifying new Deltaretroviruses. (+info)
A recurrent stop-codon mutation in succinate dehydrogenase subunit B gene in normal peripheral blood and childhood T-cell acute leukemia.
(3/266)
BACKGROUND: Somatic cytidine mutations in normal mammalian nuclear genes occur during antibody diversification in B lymphocytes and generate an isoform of apolipoprotein B in intestinal cells by RNA editing. Here, I describe that succinate dehydrogenase (SDH; mitochondrial complex II) subunit B gene (SDHB) is somatically mutated at a cytidine residue in normal peripheral blood mononuclear cells (PBMCs) and T-cell acute leukemia. Germ line mutations in the SDHB, SDHC or SDHD genes cause hereditary paraganglioma (PGL) tumors which show constitutive activation of homeostatic mechanisms induced by oxygen deprivation (hypoxia). PRINCIPAL FINDINGS: To determine the prevalence of a mutation identified in the SDHB mRNA, 180 samples are tested. An SDHB stop-codon mutation c.136C>T (R46X) is present in a significant fraction (average = 5.8%, range = less than 1 to 30%, n = 52) of the mRNAs obtained from PBMCs. In contrast, the R46X mutation is present in the genomic DNA of PBMCs at very low levels. Examination of the PBMC cell-type subsets identifies monocytes and natural killer (NK) cells as primary sources of the mutant transcript, although lesser contributions also come from B and T lymphocytes. Transcript sequence analyses in leukemic cell lines derived from monocyte, NK, T and B cells indicate that the mutational mechanism targeting SDHB is operational in T-cell acute leukemia. Accordingly, substantial levels (more than 3%) of the mutant SDHB transcripts are detected in five of 20 primary childhood T-cell acute lymphoblastic leukemia (T-ALL) bone marrow samples, but in none of 20 B-ALL samples. In addition, distinct heterozygous SDHB missense DNA mutations are identified in Jurkat and TALL-104 cell lines which are derived from T-ALLs. CONCLUSIONS: The identification of a recurrent, inactivating stop-codon mutation in the SDHB gene in normal blood cells suggests that SDHB is targeted by a cytidine deaminase enzyme. The SDHB mutations in normal PBMCs and leukemic T cells might play a role in cellular pre-adaptation to hypoxia. (+info)
Co-injection strategies to modify radiation sensitivity and tumor initiation in transgenic Zebrafish.
(4/266)
Does TAL-1 deletion contribute to the high incidence of T-cell acute lymphoblastic leukemia in South Indian patients?
(5/266)
BACKGROUND: The incidence of T-cell acute lymphoblastic leukemia (T-ALL) in South India is very high (43.1%) when compared to the Western countries (10-20%). TAL-1 deletion is the most common genetic abnormality in T-ALL. OBJECTIVES: The present study was aimed to detect the incidence of type 1 and type 2 TAL-1 deletions and assess whether they might contribute to the high incidence of T-ALL in South India. MATERIALS AND METHODS: 45 cases of T-ALL (pediatric-32, adolescents-7 and young adults-6) were studied by DNA-PCR and sequencing. Age of the patients ranged from 3 yrs to 29 yrs (median age 14 yrs). RESULTS: TAL-1 deletion type 1 was detected in 6 (13.3%) cases (3 pediatric and 3 adolescents) and all were males. TAL-1 deletion type 2 was not present. Comparing the clinical features and immunological marker analysis of TAL-1 deletion positive and negative cases did not show any significant differences except in the WBC count, which was significantly higher in cases showing TAL-1 deletion (>100 x 109/L, p value= 0.003). All the positive cases of TAL-1 deletion were confirmed by sequencing, the results showing that the fusion region at SIL gene and TAL-1 gene contained an average 'N region' insertion of 7.8 nucleotides. The numbers of nucleotides deleted at the 5' end and 3' end of TAL-1 gene were averages of 3 and 1, respectively. CONCLUSION: Though the incidence of T-ALL is high in South India, the frequency of TAL-1 deletion and their fusion gene sequences are not unique and are similar to those reported in other ethnic and geographic populations. Hence the present study indicates that TAL-1 deletion alone does not contribute to the high incidence of T-ALL in South Indian patients. (+info)
FDA drug approval summary: nelarabine (Arranon) for the treatment of T-cell lymphoblastic leukemia/lymphoma.
(6/266)