PubMed Health⌕ Search

PubMed · 9604993

Helper T lymphocyte precursor frequency analysis in alloreactivity detection.

Abstract

The utility of IL-2 secreting helper T lymphocyte precursors (HTLp) frequency testing has been evaluated for detecting alloreactivity. The frequency of HTLp was approached by limiting dilution assay. High HTLp frequency was detected in 20 out of 30 HLA matched unrelated pairs (67%). The comparison of HTLp and CTLp (cytotoxic T lymphocyte precursors) frequencies in HLA matched unrelated pairs showed that the two examinations are not fully alternative in detecting alloreactivity. This could suggest the utility of combined testing of both HTLp and CTLp frequencies for alloreactivity assessment. In contrast, five positive HTLp values were only found among 28 HLA genotypic identical siblings (18%). Previous CTLp limiting dilution studies showed very low or undetectable CTLp frequency results in that group. For that, HTLp assay remains to be the only cellular in vitro technique detecting alloreactivity in these combinations.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

V Cukrová, L Dolezalová, M Loudová, A Vítek. 1998. Helper T lymphocyte precursor frequency analysis in alloreactivity detection.. https://pubmed.ncbi.nlm.nih.gov/9604993/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Single cell mutational analysis of PIK3CA in circulating tumor cells and metastases in breast cancer reveals heterogeneity, discordance, and mutation persistence in cultured disseminated tumor cells from bone marrow.

BACKGROUND: Therapeutic decisions in cancer are generally guided by molecular biomarkers or, for some newer therapeutics, primary tumor genotype. However, because biomarkers or genotypes may change as new metastases emerge, circulating tumor cells (CTCs) from blood are being investigated for a role in guiding real-time drug selection during disease progression, expecting that CTCs will comprehensively represent the full spectrum of genomic changes in metastases. However, information is limited regarding mutational heterogeneity among CTCs and metastases in breast cancer as discerned by single cell analysis. The presence of disseminated tumor cells (DTCs) in bone marrow also carry prognostic significance in breast cancer, but with variability between CTC and DTC detection. Here we analyze a series of single tumor cells, CTCs, and DTCs for PIK3CA mutations and report CTC and corresponding metastatic genotypes. METHODS: We used the MagSweeper, an immunomagnetic separation device, to capture live single tumor cells from breast cancer patients' primary and metastatic tissues, blood, and bone marrow. Single cells were screened for mutations in exons 9 and 20 of the PIK3CA gene. Captured DTCs grown in cell culture were also sequenced for PIK3CA mutations. RESULTS: Among 242 individual tumor cells isolated from 17 patients and tested for mutations, 48 mutated tumor cells were identified in three patients. Single cell analyses revealed mutational heterogeneity among CTCs and tumor cells in tissues. In a patient followed serially, there was mutational discordance between CTCs, DTCs, and metastases, and among CTCs isolated at different time points. DTCs from this patient propagated in vitro contained a PIK3CA mutation, which was maintained despite morphological changes during 21 days of cell culture. CONCLUSIONS: Single cell analysis of CTCs can demonstrate genotypic heterogeneity, changes over time, and discordance from DTCs and distant metastases. We present a cautionary case showing that CTCs from any single blood draw do not always reflect metastatic genotype, and that CTC and DTC analyses may provide independent clinical information. Isolated DTCs remain viable and can be propagated in culture while maintaining their original mutational status, potentially serving as a future resource for investigating new drug therapies.

Bone Marrow↗

Trisomy 8 as sole cytogenetic abnormality in a case of chronic lymphocytic leukemia.

A 49-year-old man, who had been diagnosed with chronic lymphocytic leukemia (CLL) in 2002, had a normal karyotype in his bone marrow. Trisomy 8 was demonstrated in his peripheral blood in 2005. Fluorescence in situ hybridization using an LSI CEP 8 probe performed on the archival bone marrow specimen showed three hybridization signals in 40% of 200 interphase cells scored. This confirmed that the trisomy 8 abnormality was present in both the blood and bone marrow samples. Trisomy 8 as the sole chromosomal abnormality in CLL is a very rare finding. The prognostic significance of trisomy 8 in CLL remains to be seen.

Bone Marrow↗