Mono/oligoclonal T and NK cells are common in chronic myeloid leukemia patients at diagnosis and expand during dasatinib therapy
(2010) In Blood 116(5). p.772-782- Abstract
- In a proportion of patients with chronic myeloid leukemia (CML) being treated with dasatinib, we recently observed large granular lymphocyte (LGL) expansions carrying clonal T-cell receptor (TCR) gamma/delta gene rearrangements. To assess the prevalence and role of clonal lymphocytes in CML, we collected samples from patients (n = 34) at the time of diagnosis and during imatinib and dasatinib therapies and analyzed lymphocyte clonality with a sensitive polymerase chain reaction-based method of TCR gamma and delta genes. Surprisingly, at CML diagnosis, 15 of 18 patients (83%) had a sizeable clonal, BCR-ABL1 negative lymphocyte population, which was uncommon in healthy persons (1 of 12; 8%). The same clone persisted at low levels in most... (More)
- In a proportion of patients with chronic myeloid leukemia (CML) being treated with dasatinib, we recently observed large granular lymphocyte (LGL) expansions carrying clonal T-cell receptor (TCR) gamma/delta gene rearrangements. To assess the prevalence and role of clonal lymphocytes in CML, we collected samples from patients (n = 34) at the time of diagnosis and during imatinib and dasatinib therapies and analyzed lymphocyte clonality with a sensitive polymerase chain reaction-based method of TCR gamma and delta genes. Surprisingly, at CML diagnosis, 15 of 18 patients (83%) had a sizeable clonal, BCR-ABL1 negative lymphocyte population, which was uncommon in healthy persons (1 of 12; 8%). The same clone persisted at low levels in most imatinib-treated patients. In contrast, in a distinct population of dasatinib-treated patients, the diagnostic phase clone markedly expanded, resulting in absolute lymphocytosis in blood. Most patients with LGL expansions (90%) had TCR delta rearrangements, which were uncommon in patients without an LGL expansion (10%). The TCR delta clones were confined to gamma delta(+) T- or natural killer-cell compartments and the TCR gamma clones to CD4(+)/CD8(+) alpha beta(+) fractions. The functional importance of clonal lymphocytes as a part of leukemia immune surveillance and the putative anergy- reversing role of dasatinib require further evaluation. (Blood. 2010; 116(5): 772- 782) (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1678506
- author
- Kreutzman, Anna ; Juvonen, Vesa ; Kairisto, Veli ; Ekblom, Marja LU ; Stenke, Leif ; Seggewiss, Ruth ; Porkka, Kimmo and Mustjoki, Satu
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Blood
- volume
- 116
- issue
- 5
- pages
- 772 - 782
- publisher
- American Society of Hematology
- external identifiers
-
- wos:000280596500017
- scopus:77956280601
- pmid:20413659
- ISSN
- 1528-0020
- DOI
- 10.1182/blood-2009-12-256800
- language
- English
- LU publication?
- yes
- id
- 45d6423b-863f-4cdc-976a-89d8d406010a (old id 1678506)
- date added to LUP
- 2016-04-01 10:09:03
- date last changed
- 2022-07-28 20:13:31
@article{45d6423b-863f-4cdc-976a-89d8d406010a,
abstract = {{In a proportion of patients with chronic myeloid leukemia (CML) being treated with dasatinib, we recently observed large granular lymphocyte (LGL) expansions carrying clonal T-cell receptor (TCR) gamma/delta gene rearrangements. To assess the prevalence and role of clonal lymphocytes in CML, we collected samples from patients (n = 34) at the time of diagnosis and during imatinib and dasatinib therapies and analyzed lymphocyte clonality with a sensitive polymerase chain reaction-based method of TCR gamma and delta genes. Surprisingly, at CML diagnosis, 15 of 18 patients (83%) had a sizeable clonal, BCR-ABL1 negative lymphocyte population, which was uncommon in healthy persons (1 of 12; 8%). The same clone persisted at low levels in most imatinib-treated patients. In contrast, in a distinct population of dasatinib-treated patients, the diagnostic phase clone markedly expanded, resulting in absolute lymphocytosis in blood. Most patients with LGL expansions (90%) had TCR delta rearrangements, which were uncommon in patients without an LGL expansion (10%). The TCR delta clones were confined to gamma delta(+) T- or natural killer-cell compartments and the TCR gamma clones to CD4(+)/CD8(+) alpha beta(+) fractions. The functional importance of clonal lymphocytes as a part of leukemia immune surveillance and the putative anergy- reversing role of dasatinib require further evaluation. (Blood. 2010; 116(5): 772- 782)}},
author = {{Kreutzman, Anna and Juvonen, Vesa and Kairisto, Veli and Ekblom, Marja and Stenke, Leif and Seggewiss, Ruth and Porkka, Kimmo and Mustjoki, Satu}},
issn = {{1528-0020}},
language = {{eng}},
number = {{5}},
pages = {{772--782}},
publisher = {{American Society of Hematology}},
series = {{Blood}},
title = {{Mono/oligoclonal T and NK cells are common in chronic myeloid leukemia patients at diagnosis and expand during dasatinib therapy}},
url = {{http://dx.doi.org/10.1182/blood-2009-12-256800}},
doi = {{10.1182/blood-2009-12-256800}},
volume = {{116}},
year = {{2010}},
}