Effect of chemotherapy and stem cell transplantation on T lymphocyte clones in familial haemophagocytic lymphohistiocytosis

Nobuhiro Kimura, Eiichi Ishii, Masahiro Sako, Tetsuya Yoshida, Mitsuyuki Nagano, Hidetoshi Takada, Shinsaku Imashuku, Kazuo Tamura

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Familial haemophagocytic lymphohistiocytosis (FHL) is a rare disorder in infancy, curative only by an allogeneic stem cell transplantation (SCT). We recently confirmed the clonal evidence of T cells in FHL. To confirm the effect of chemotherapy and SCT in FHL, the change of T-cell clones was analysed in two patients using inverse reverse transcription-polymerase chain reaction (RT-PCR) of the T-cell receptor variable region (TCRV) gene, followed by PCR for the junctional region (Jβ-PCR), a single-strand conformation polymorphism (SSCP) and sequencing analysis at diagnosis, after chemotherapy and after SCT. A high frequency (> 15%) of αβ T-cell clones and a predominant bias (Jβ1:Jβ2, 85:15) for the Jβ1 subgroup were observed in the two patients at diagnosis. In one patient, however, an inverted predominant bias (Jβ1:Jβ2, 9:91) for the Jβ2 subgroup and oligoclonal expansion were observed at relapse after chemotherapy. In the other patient, correction of both restricted Jβ cluster usage and variation of TCR were observed after chemotherapy and SCT. Using sequence analysis, the clonal T cells detected at diagnosis were found to be substituted at low frequency (< 0.75%) by several new clones after chemotherapy and SCT. These results indicate that any genetic defect could influence the regulation of the T-cell network, and normalization of both the variation in each Vβ repertoire and the Jβ1/Jβ2 ratio is needed to achieve remission, and might support the rationale that the only acceptable curative therapy of FHL is allogeneic SCT.

Original languageEnglish
Pages (from-to)822-831
Number of pages10
JournalBritish Journal of Haematology
Volume113
Issue number3
DOIs
Publication statusPublished - Jun 21 2001

Fingerprint

Hemophagocytic Lymphohistiocytosis
Stem Cell Transplantation
Clone Cells
T-Lymphocytes
Drug Therapy
Polymerase Chain Reaction
T-Cell Antigen Receptor
Reverse Transcription
Sequence Analysis
Recurrence
Genes

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Effect of chemotherapy and stem cell transplantation on T lymphocyte clones in familial haemophagocytic lymphohistiocytosis. / Kimura, Nobuhiro; Ishii, Eiichi; Sako, Masahiro; Yoshida, Tetsuya; Nagano, Mitsuyuki; Takada, Hidetoshi; Imashuku, Shinsaku; Tamura, Kazuo.

In: British Journal of Haematology, Vol. 113, No. 3, 21.06.2001, p. 822-831.

Research output: Contribution to journalArticle

Kimura, Nobuhiro ; Ishii, Eiichi ; Sako, Masahiro ; Yoshida, Tetsuya ; Nagano, Mitsuyuki ; Takada, Hidetoshi ; Imashuku, Shinsaku ; Tamura, Kazuo. / Effect of chemotherapy and stem cell transplantation on T lymphocyte clones in familial haemophagocytic lymphohistiocytosis. In: British Journal of Haematology. 2001 ; Vol. 113, No. 3. pp. 822-831.
@article{13f2faa71b5e4aa9af741fe6655476c2,
title = "Effect of chemotherapy and stem cell transplantation on T lymphocyte clones in familial haemophagocytic lymphohistiocytosis",
abstract = "Familial haemophagocytic lymphohistiocytosis (FHL) is a rare disorder in infancy, curative only by an allogeneic stem cell transplantation (SCT). We recently confirmed the clonal evidence of T cells in FHL. To confirm the effect of chemotherapy and SCT in FHL, the change of T-cell clones was analysed in two patients using inverse reverse transcription-polymerase chain reaction (RT-PCR) of the T-cell receptor variable region (TCRV) gene, followed by PCR for the junctional region (Jβ-PCR), a single-strand conformation polymorphism (SSCP) and sequencing analysis at diagnosis, after chemotherapy and after SCT. A high frequency (> 15{\%}) of αβ T-cell clones and a predominant bias (Jβ1:Jβ2, 85:15) for the Jβ1 subgroup were observed in the two patients at diagnosis. In one patient, however, an inverted predominant bias (Jβ1:Jβ2, 9:91) for the Jβ2 subgroup and oligoclonal expansion were observed at relapse after chemotherapy. In the other patient, correction of both restricted Jβ cluster usage and variation of TCR were observed after chemotherapy and SCT. Using sequence analysis, the clonal T cells detected at diagnosis were found to be substituted at low frequency (< 0.75{\%}) by several new clones after chemotherapy and SCT. These results indicate that any genetic defect could influence the regulation of the T-cell network, and normalization of both the variation in each Vβ repertoire and the Jβ1/Jβ2 ratio is needed to achieve remission, and might support the rationale that the only acceptable curative therapy of FHL is allogeneic SCT.",
author = "Nobuhiro Kimura and Eiichi Ishii and Masahiro Sako and Tetsuya Yoshida and Mitsuyuki Nagano and Hidetoshi Takada and Shinsaku Imashuku and Kazuo Tamura",
year = "2001",
month = "6",
day = "21",
doi = "10.1046/j.1365-2141.2001.02784.x",
language = "English",
volume = "113",
pages = "822--831",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Effect of chemotherapy and stem cell transplantation on T lymphocyte clones in familial haemophagocytic lymphohistiocytosis

AU - Kimura, Nobuhiro

AU - Ishii, Eiichi

AU - Sako, Masahiro

AU - Yoshida, Tetsuya

AU - Nagano, Mitsuyuki

AU - Takada, Hidetoshi

AU - Imashuku, Shinsaku

AU - Tamura, Kazuo

PY - 2001/6/21

Y1 - 2001/6/21

N2 - Familial haemophagocytic lymphohistiocytosis (FHL) is a rare disorder in infancy, curative only by an allogeneic stem cell transplantation (SCT). We recently confirmed the clonal evidence of T cells in FHL. To confirm the effect of chemotherapy and SCT in FHL, the change of T-cell clones was analysed in two patients using inverse reverse transcription-polymerase chain reaction (RT-PCR) of the T-cell receptor variable region (TCRV) gene, followed by PCR for the junctional region (Jβ-PCR), a single-strand conformation polymorphism (SSCP) and sequencing analysis at diagnosis, after chemotherapy and after SCT. A high frequency (> 15%) of αβ T-cell clones and a predominant bias (Jβ1:Jβ2, 85:15) for the Jβ1 subgroup were observed in the two patients at diagnosis. In one patient, however, an inverted predominant bias (Jβ1:Jβ2, 9:91) for the Jβ2 subgroup and oligoclonal expansion were observed at relapse after chemotherapy. In the other patient, correction of both restricted Jβ cluster usage and variation of TCR were observed after chemotherapy and SCT. Using sequence analysis, the clonal T cells detected at diagnosis were found to be substituted at low frequency (< 0.75%) by several new clones after chemotherapy and SCT. These results indicate that any genetic defect could influence the regulation of the T-cell network, and normalization of both the variation in each Vβ repertoire and the Jβ1/Jβ2 ratio is needed to achieve remission, and might support the rationale that the only acceptable curative therapy of FHL is allogeneic SCT.

AB - Familial haemophagocytic lymphohistiocytosis (FHL) is a rare disorder in infancy, curative only by an allogeneic stem cell transplantation (SCT). We recently confirmed the clonal evidence of T cells in FHL. To confirm the effect of chemotherapy and SCT in FHL, the change of T-cell clones was analysed in two patients using inverse reverse transcription-polymerase chain reaction (RT-PCR) of the T-cell receptor variable region (TCRV) gene, followed by PCR for the junctional region (Jβ-PCR), a single-strand conformation polymorphism (SSCP) and sequencing analysis at diagnosis, after chemotherapy and after SCT. A high frequency (> 15%) of αβ T-cell clones and a predominant bias (Jβ1:Jβ2, 85:15) for the Jβ1 subgroup were observed in the two patients at diagnosis. In one patient, however, an inverted predominant bias (Jβ1:Jβ2, 9:91) for the Jβ2 subgroup and oligoclonal expansion were observed at relapse after chemotherapy. In the other patient, correction of both restricted Jβ cluster usage and variation of TCR were observed after chemotherapy and SCT. Using sequence analysis, the clonal T cells detected at diagnosis were found to be substituted at low frequency (< 0.75%) by several new clones after chemotherapy and SCT. These results indicate that any genetic defect could influence the regulation of the T-cell network, and normalization of both the variation in each Vβ repertoire and the Jβ1/Jβ2 ratio is needed to achieve remission, and might support the rationale that the only acceptable curative therapy of FHL is allogeneic SCT.

UR - http://www.scopus.com/inward/record.url?scp=0034990781&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034990781&partnerID=8YFLogxK

U2 - 10.1046/j.1365-2141.2001.02784.x

DO - 10.1046/j.1365-2141.2001.02784.x

M3 - Article

C2 - 11380476

AN - SCOPUS:0034990781

VL - 113

SP - 822

EP - 831

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 3

ER -