The naive T‐lymphocyte compartment is well preserved in patients with chronic myelogenous leukaemia in chronic phase

Isoda, Atsushi; Yokohama, Akihiko; Maekawa, Takafumi; Tsukamoto, Norifumi; Nojima, Yoshihisa; Karasawa, Masamitsu

doi:10.1046/j.1365-2141.2002.03943.x

Cited by 10 publications

(10 citation statements)

References 40 publications

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“…2A) were within the range reported by other authors for healthy subjects belonging to this age group (Isoda et al, 2002). We found a significantly diminished amount of CD4 ϩ naïve T cells in AT heterozygotes versus normal donors (p Ͻ 0.01), with only one heterozygous subject (Ht16-m, Fig.…”

Section: Lantelme Et Alsupporting

confidence: 71%

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Analysis of Secondary V(D)J Rearrangements in Mature, Peripheral T Cells of Ataxia-Telangiectasia Heterozygotes

Lantelme

Turinetto

Mantovani

et al. 2003

Laboratory Investigation

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SUMMARY:Ataxia-telangiectasia (AT) is a rare recessive disease with pleiotropic involvement of the nervous and lymphoid systems. AT heterozygotes have a population frequency of about 1%, and although not manifesting any overt clinical symptoms, they have an increased mortality, mainly because of cancer and ischemic heart disease. We and others have described a mature T lymphocyte population with an altered T cell receptor surface expression ("TCR variant") that reactivates the recombination activating genes (RAG) and is expanded in the blood of patients with AT. In view of the known role of V(D)J recombination in the onset of tumorigenic translocations, we proposed that the increased RAG activity was responsible for the predisposition of AT homozygotes to develop mature-type T leukemia/lymphoma. In the present report, we used cytofluorimetry to quantify the TCR variant population and the memory/naïve T-cell compartments in the blood of AT heterozygotes compared with AT patients and controls. We assessed the expression of different recombinase genes through RT-PCR/oligotyping and cytofluorometric analysis and searched for rearrangement intermediates by ligase-mediated PCR in T-cell lines from four heterozygous carriers. We found the TCR variant population was increased on average 2ϫ in AT heterozygotes (vs 10ϫ in homozygotes) compared with controls, and naïve CD4 ϩ T lymphocytes were reduced on average 0.5ϫ (vs 0.1ϫ in homozygotes). We were able to demonstrate recombinase gene expression in all four heterozygous T-cell lines, and rearrangement intermediates, indicative of ongoing V(D)J recombination, in two. These rearrangements were compatible with V-gene replacement, a mechanism of receptor editing described for Ig and TCR␣ genes, to our knowledge not previously documented for TCR␤. In conclusion, we found that RAG reactivation and secondary V(D)J rearrangements, potential risk factors of mature-type leukemia in AT homozygotes, also take place in AT heterozygous carriers and might place this large population fraction at an increased risk of leukemia/lymphoma. (Lab Invest 2003, 83:1467-1475. E vidence supports the existence among peripheral T lymphocytes of a variant subpopulation with an altered TCR surface expression (CD4 ϩ CD3 low ) in which recombination activating genes (RAG) are expressed. We and others observed functional RAG gene products in mature T cells with defective TCR expression (Lantelme et al, 2000b;McMahan and Fink, 1998), and we showed that these T cells were increased in number in patients with ataxiatelangiectasia (AT) and Nijmegen breakage syndrome (Lantelme et al, 2000a), both autosomal recessive chromosomal instability syndromes characterized by immunodeficiency, hypersensitivity to ionizing radiation, defective DNA repair, and predisposition to develop lymphoid malignancies (Lavin and Shiloh, 1997;Shiloh, 1997). The finding of RAG gene expression in this TCR variant subpopulation suggests that secondary V(D)J rearrangements may occur physiologically to rescue their defective phenotype a...

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Section: Lantelme Et Alsupporting

confidence: 71%

“…Again, we found that the CD8 naïve compartment in four AT heterozygotes as well as in three age-matched control subjects (Fig. 2B) was comprised within the mean value reported by Isoda et al (2002) for healthy subjects belonging to the same age group (mean Ϯ SD, 41 Ϯ 26.8%). …”

mentioning

confidence: 63%

Analysis of Secondary V(D)J Rearrangements in Mature, Peripheral T Cells of Ataxia-Telangiectasia Heterozygotes

Lantelme

Turinetto

Mantovani

et al. 2003

Laboratory Investigation

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“…At least in the case of CML, the decrease was unlikely to be caused by a reduction in the number of CD8 + leukocytes. In fact, CD8 + /CD3 + T cell ratios at different stages of CML are generally not reduced compared with those in healthy donors [45,46]. Our results also demonstrate that the intensity of the FCRL6 hybridization signals was decreased in PBMCs and CD3 + cells from patients with autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and idiopathic thrombocytopenia purpura.…”

Section: Discussionsupporting

confidence: 41%

FCRL6 receptor: Expression and associated proteins

et al. 2011

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“…In CML, the percentage of CD4+ cells is high compared to the control group in an untreated state and rapidly decreases after treatment. In contrast, the proportion of CD8 cells remains much the same throughout treatment [16]. The pathophysiology of the cutaneous manifestations to STI 571 is unclear, but as mentioned above, the increased CD8+ cell proportion with CML treatment may explain the intense cutaneous infiltration of CD8+ cells at the drug eruption site.…”

Section: Discussionmentioning

confidence: 81%