Aggressive T-Cell LGL Leukemia

2009 ◽  
pp. 49-49
Author(s):  
Hubert Scharnagl ◽  
Winfried März ◽  
Markus Böhm ◽  
Thomas A. Luger ◽  
Federico Fracassi ◽  
...  
Keyword(s):  
T Cell ◽  
Lgl Leukemia

scholarly journals Detection of human T-cell leukemia/lymphoma virus, type II, in a patient with large granular lymphocyte leukemia

Blood ◽  
1992 ◽  
Vol 80 (5) ◽  
pp. 1116-1119 ◽  
Author(s):  
TP Jr Loughran ◽  
T Coyle ◽  
MP Sherman ◽  
G Starkebaum ◽  
GD Ehrlich ◽  
...  
Keyword(s):  
T Cell ◽  
Large Granular Lymphocyte ◽  
Enzyme Linked Immunosorbent Assay ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Enzymatic Amplification ◽  
Htlv Infection ◽  
Human T Cell ◽  
Polymerase Chain ◽  
Lgl Leukemia

Abstract We studied a patient with large granular lymphocyte (LGL) leukemia for evidence of human T-cell leukemia/lymphoma virus (HTLV) infection. Serum from this patient was positive for HTLV-I/II antibodies by enzyme- linked immunosorbent assay (ELISA) and was confirmed positive in Western blot and radioimmunoprecipitation assays. Results of a synthetic peptide-based ELISA showed that the seropositivity was caused by HTLV-II and not HTLV-I infection. Analyses of enzymatic amplification of DNA from bone marrow sections using the polymerase chain reaction (PCR) were positive for HTLV-II specific gag, pol, env, and pX gene sequences. Cloning and sequencing of amplified products showed that the HTLV-II pol and pX sequences in patient DNA differed from the sequences of 17 other HTLV-II isolates examined in our laboratory. HTLV infection may have a role in some patients in the pathogenesis of LGL leukemia.

scholarly journals Lack of gene rearrangement and mRNA expression of the beta chain of the T cell receptor in spontaneous rat large granular lymphocyte leukemia lines.

1985 ◽  
Vol 161 (5) ◽  
pp. 1249-1254 ◽  
Author(s):  
C W Reynolds ◽  
M Bonyhadi ◽  
R B Herberman ◽  
H A Young ◽  
S M Hedrick
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Antigen Receptor ◽  
Cell Receptor ◽  
Large Granular Lymphocyte ◽  
Beta Chain ◽  
T Cell Antigen Receptor ◽  
Cell Antigen Receptor ◽  
Cell Antigen ◽  
Lgl Leukemia

Using the murine cDNA clone for the beta chain of the T cell antigen receptor, we have examined four highly cytotoxic rat large granular lymphocyte (LGL) leukemia lines for the expression of unique rearrangements and mRNA transcription of the genes coding for the T cell antigen receptor. In contrast to normal rat T cells and nine rat T cell lines, the LGL leukemia lines exhibited no detectable gene rearrangements in the beta chain locus after digestion of LGL DNA by four restriction enzymes. Northern blots containing RNA from these LGL tumor lines demonstrated a low level of aberrant or nonrearranged beta chain transcription (less than 10 copies per cell) but virtually no translatable 1.3 kilobase message. These results demonstrate that LGL leukemia lines which mediate both natural killer (NK) and antibody-dependent cell-mediated cytotoxicity (ADCC) activities do not express the beta chain of the T cell receptor. The nature of the NK cell receptor for antigen remains elusive.

scholarly journals Deep sequencing of the T-cell receptor repertoire in CD8+ T-large granular lymphocyte leukemia identifies signature landscapes

Blood ◽  
2013 ◽  
Vol 122 (25) ◽  
pp. 4077-4085 ◽  
Author(s):  
Michael J. Clemente ◽  
Bartlomiej Przychodzen ◽  
Andres Jerez ◽  
Brittney E. Dienes ◽  
Manuel G. Afable ◽  
...  
Keyword(s):  
T Cell ◽  
Deep Sequencing ◽  
Cell Receptor ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Receptor Repertoire ◽  
Key Points ◽  
T Cell Receptor Repertoire ◽  
Cell Receptor Repertoire ◽  
Lgl Leukemia

Key PointsT-cell repertoire deep sequencing clearly identifies the nucleotide and amino acid sequence of the immunodominant clone in T-LGL leukemia patients. Deep-sequencing results suggest that CD8+ T-LGL leukemia is characterized by specific CDR3 clonotypes that are private to the disease.

Polarized CTL Responses Detected in Patients with Autoimmune Neutropenia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1459-1459
Author(s):  
Marcin W. Wlodarski ◽  
Yadira Narvaez ◽  
Alexander Rodriquez ◽  
Jaroslaw P. Maciejewski
Keyword(s):  
Flow Cytometry ◽  
T Cell ◽  
Significant Proportion ◽  
Diagnostic Algorithm ◽  
Diagnostic Methods ◽  
Cytotoxic T Cell ◽  
Autoimmune Neutropenia ◽  
Pcr Cloning ◽  
Myeloid Progenitor Cells ◽  
Lgl Leukemia

Abstract Drugs and intrinsic bone marrow diseases can explain most of the cases of neutropenia, and true autoimmune neutropenia (AIN) is a diagnosis of exclusion. Anti-neutrophil antibodies are not reliable, and their absence does not preclude the diagnosis of AIN. Lineage-restricted cytopenias, including neutropenia, were associated with T cell Large Granular Lymphocyte leukemia (T-LGL), but the diagnosis of this condition involves positive TCR rearrangement and flow cytometric identification of a pathologic cytotoxic T cell (CTL) population. These routinely applied methods have a limited sensitivity and rely on the presence of a high frequency of clonal cells in the sample. AIN, similar to T-LGL, may be related to a CTL-mediated process. We hypothesize that AIN, in a portion of patients, is a CTL-mediated disease in which myeloid progenitor cells are the targets. Consequently, in those patients, polarized expansions of CTL clones may be detected if efficient and sensitive diagnostic methods will be applied. Previously, we developed a diagnostic algorithm for the identification and quantification of clonal expansions in T-LGL based on the molecular analysis of TCR- utilization pattern. We studied a cohort of patients with various degrees of neutropenia (N=23) that was unexplained by clinical grounds and standard laboratory testing. Anti-neutrophil antibodies were found in 6 of these patients; in 3 patients, serum-mediated inhibition (>20%) of colony formation by normal hematopoietic progenitor was found, but there was no correlation between antibodies and serum inhibition. For detection of CTL expansions in AIN, VB typing and VB specific RT-PCR were applied followed by PCR cloning and sequencing of a large number of clones, and determination of expanded CDR3 clonotypes. When no expansion was detected by flow cytometry, multiplex PCR was used to amplify the whole VB spectrum. If identical CDR3 regions were detected by sequencing of at least 22 clones, CDR3 fragments of appropriate VB families were subcloned and sequenced, and immunodominant (identical clones occurring repetitively) were identified. Using this approach, we found only 2 expanded clones in 24 healthy donors. Those expanded clones accounted for 20% of a given VB family, or 0.7% of the CD8+ repertoire (as calculated by multiplication of clonal expansion within VB family by VB family contribution to the whole CTL population). In AIN we found expansion in 9 of 21 patients (3 of them were not detected by VB flow cytometry). Clonal frequency was 40%± 13% of a given VB family or 13%± 14% of the total CD8+ population. The presence of expanded CTL did not correlate with anti-neutrophil antibodies of serum-mediated colony inhibition. By comparison, CTL clones found in patients with T-LGL leukemia (N=75) comprised 68% of a given VB family, or 43% of the entire VB repertoire. We conclude that, using sensitive approaches, CTL expansions can be detected in a significant proportion of patients with AIN. These cases may represent minor variants of an autoimmune process that operates in T-LGL leukemia. The antigens that trigger these expansions likely may be shared. Clinically, detection of the CTL-mediated process in neutropenia may point toward rational immunosuppressive therapy aimed at T cells.

T Large Granular Lymphocyte (LGL) Leukemia Characterized by Expansion of Terminal CD3+/CD8+/CD62L−/CD45RA+ Effector Memory T Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4962-4962
Author(s):  
JianXiang Zou ◽  
Jeffrey S. Painter ◽  
Fanqi Bai ◽  
Thomas P. Loughran ◽  
P.K. Epling-Burnette
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Memory T Cells ◽  
Effector Memory ◽  
T Cell Proliferation ◽  
Normal Controls ◽  
Terminal Effector ◽  
Homeostatic Mechanisms ◽  
Lgl Leukemia

Abstract Background: Clonal proliferation by mature Large Granular Lymphocytes is associated with LGL leukemia. This expansion of CD3− NK cells or CD3+ T cells may be the result of chronic antigen stimulation by autoantigens or viral antigens. In association with T cell lymphoproliferation, approximately 45% of patients with LGL leukemia have severe neutropenia (absolute neutrophil count <0.5×109/L) and 20% of patients have transfusion-dependent anemia. Homeostatic mechanisms normally modulate the generation of naïve and memory T cell pools and regulate the T cell repertoire; however, the pathways elicited during T memory differentiation, maintenance and expansion are not fully characterized. The goal of this work was to characterize the homeostatic mechanisms that regulate LGL leukemia. Methods: Peripheral blood mononuclear cells were isolated from patients with LGL leukemia and normal controls. We performed multiplex TCR-Vβ (CDR3) PCR on cells from 16 LGL patients to identify clonal T cell proliferation. The percentage of CD3+ T cells that expressed each of the TCR-Vβ families was determined in 20 healthy donors to establish the mean and standard deviation (S.D.) of the control population. Naïve and memory CD4 and CD8 T cell sub-populations were segregated by expression of CD45RA and CD62L expression by flow cytometry and T cell proliferation was assessed by Brdu incorporation in CD4+ and CD8+ T cells. Results: The absolute number of CD4+ T cells was reduced in LGL patients compared to normal donors and T cell clones were characterized by a CD8+ phenotype. By flow cytometry, expansion of a single Vβ clonal population occurred in 8 of 16 patients (50%), two clones were present in 4 of 16 patients (25%), and three clones in 4 of 16 patients (25%). The immunophenotype of TCR Vβ+ clonal T cells was CD8 positive, CD57 positive, CD28 negative, CD25 negative, and NKG2D (NKG2-family) positive and CD244 (2B4) positive. Three patients examined expressed Killer-Immunoglobulin-like (KIR) receptors. Further phenotype analysis showed that there were fewer than normal CD4+ naïve (CD4+/CD45RA+/CD62L+) T cells (23%±16 vs. 41%± 15, P=0.04 by a t test) in LGL patients. CD4+ T cells from patients had reduced proliferation in response to antigen stimulation. The reduction in CD4+ naïve T cells was associated with increased percentages of CD4+/CD45RA−/CD62L+ central memory T cells (P<0.05). Reduced percentage of naive CD8+ T cells in detected in LGL leukemia patients. In addition, CD4+ central memory cells were also significantly reduced in patients. CD8+ T cells were primarily characterized by a CD45RA+/CD62L− terminal effector memory phenotype that was significantly increased compared to normal donors (mean 75% ± 13 in patients vs 30% ± 13 in normal controls, P<0.0001). In the presence of a skewed repertoire and terminal effector memory cell accumulation, antigen-induced proliferation of CD8+ T cells in LGL did not differ from normal controls (13% ± 11 in patients vs. 9% ± 3 in normal controls, P=0.3). Conclusions: These results suggest that leukemic LGL represent the accumulation of CD8+ terminal effector memory cells with the capacity for increased proliferation. Our findings suggest that normal homeostatic signals are impaired in LGL leukemia that limits the terminal CD8 differentiation phase of an immune response.

Large Granular Lymphocyte Leukemia: Clonality Reconsidered.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3102-3102
Author(s):  
Wesley Witteles ◽  
Bing Zhang ◽  
Iris Schrijver ◽  
Daniel Arber ◽  
Jason Gotlib ◽  
...  
Keyword(s):  
Capillary Electrophoresis ◽  
T Cell ◽  
High Resolution ◽  
Clinical Characteristics ◽  
Cell Receptor ◽  
Concordance Rate ◽  
Large Granular Lymphocyte ◽  
Third Generation ◽  
Primer Sets ◽  
Lgl Leukemia

Abstract Background: T-cell large granular lymphocyte (LGL) leukemia is widely considered to represent a monoclonal proliferation of lymphocytes. Clonality assessment methods have evolved from Southern blots (first-generation) to polymerase chain reaction with heteroduplex electrophoresis (second-generation) to high-resolution capillary electrophoresis (third-generation) testing. Aims: To determine if third-generation T-cell clonality assays result in a higher frequency of oligoclonal results, to compare the concordance for testing at the T-cell receptor (TCR) gamma (TCRG) and TCR beta (TCRB) loci, and to compare the clinical characteristics of patients with monoclonal vs. oligoclonal TCRs. Methods: The study population consisted of patients from August 1999-April 2007 with elevated circulating LGLs and cytopenia(s). TCRG locus clonality was determined by both the heteroduplex method and capillary electrophoresis in 35 patients. 89 samples were tested for TCRG and TCRB clonality using the Biomed II PCR primer sets and capillary electrophoresis on an ABI 3100 automated DNA sequencer. Determinations of clonality were made independently by three pathologists blinded to the clinical characteristics of the patients. Results: A total of 93 patients (median age 50 years, 53% female) were evaluated. Median absolute neutrophil count was 1.56 × 109/L (range 0.2–7.8 × 109/L), median lymphocyte count was 1.81 × 109/L (range 0.6–13 × 109/L), and median hemoglobin was 13 g/dL (range 6.3–17.4 g/dL). The concordance rate for TCRG clonality testing by the heteroduplex and capillary electrophoresis methods was only 40%. The primary difference was a striking increase in the frequency of oligoclonal results by the capillary electrophoresis method (p= 0.00007). All of these samples appeared monoclonal by the lower resolution heteroduplex assay (Table 1). Concordance for clonality for TCRG vs. TCRB was 54% (Table 2). All samples had monoclonality or oligoclonality demonstrated at TCRG or TCRB, but only 26% were monoclonal at both loci. The clinical characteristics for the 23 patients with monoclonal TCRG and TCRB appeared similar to the 23 patients with oligoclonal TCRG and TCRB. The median age in both groups was 53 years, with 61% of patients in each group requiring treatment after a median of 36.8 and 38.6 months of follow-up, respectively. Discussion: The high resolution of capillary electrophoresis appears to result in a much greater proportion of oligoclonal TCRG results, which by the older heteroduplex method would have been considered monoclonal. Furthermore, the concordance rate at TCRG and TCRB appears to be remarkably low. Though oligoclonal T-cell populations are generally believed to be transient and reactive processes, the clinical characteristics of our oligoclonal and monoclonal cohorts did not differ significantly. Conclusion: Capillary electrophoresis frequently identifies patients with oligoclonal TCR whose clinical features are indistinguishable from those of patients with classic monoclonal LGL leukemia. Heteroduplex Monoclonal Negative Oligoclonal Total Monoclonal 12 1 1 14 Capillary Electrophoresis Negative 4 2 0 6 Oligoclonal 15 0 0 15 Total 31 3 1 35 TCRG Monoclonal Negative Oligoclonal Total Monoclonal 23 3 12 38 TCRB Negative 7 0 1 8 Oligoclonal 15 3 25 43 Total 45 6 38 89

High Resolution Karyotyping of Large Granular Lymphocyte Leukemia by SNP Arrays Reveals Clonal Defects Leading to LOH at Loci Integral to Lymphocyte Function.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1513-1513
Author(s):  
Aaron D. Viny ◽  
Hideki Makashima ◽  
Jungwon Huh ◽  
Karl S. Theil ◽  
Lukasz Gondek ◽  
...  
Keyword(s):  
T Cell ◽  
Copy Number ◽  
Chromosomal Abnormalities ◽  
Germ Line ◽  
Clonal Expansion ◽  
Large Granular Lymphocyte ◽  
Copy Number Loss ◽  
Snp Arrays ◽  
Large Granular Lymphocyte Leukemia ◽  
Lgl Leukemia

Abstract Large granular lymphocyte leukemia (LGL leukemia) is a semiautonomous clonal lymphoproliferation of cytotoxic T cells associated with various immune cytopenias. Within the spectrum of acquired immune-mediated bone marrow failure states, LGL leukemia can serve as monoclonal model of usually polyclonal T cell-mediated pathology. Mechanisms of unopposed clonal expansion of LGL cells in many aspects resemble true lymphoma and are not well understood. In addition to its reactive character, intrinsic clonal defects may be present in some patient with LGL, in particular those with more pronounced lymphoproliferative features. However, unlike in B-cell lymphomas, recurrent chromosomal abnormalities have not been frequently identified in LGL leukemia using traditional metaphase karyotyping techniques. We have applied Affymetrix 250K single nucleotide polymorphism-arrays (SNP-A) and 6.0 SNP-A in 28 patients with LGL leukemia, to elicit a far higher resolution of chromosomal content through genomic mapping of individual SNP and respective copy number analysis in LGL leukemia. SNP-A based cytogenetics have been applied successfully to MDS patients and has increased prognostic reliability. Blood mononuclear cells containing high proportion of clonal cells as determined by TCR Vβ flow cytometry were used as a source of DNA. For comparison, a large number of control blood and marrow specimens (N=119 for 6.0 and 124 for 250K SNP arrays) were analyzed. Data were processed using Genotyping Console v2.1 software (Affymetrix, Santa Clara, CA). After exclusion of known copy number variants (CNV) referenced in public databases and our own set of 178 normal controls, we found distinct chromosomal changes in 16/28 (57%) of LGL leukemia patients. Consensus regions of deletion/gain or uniparental disomy (UPD) were identified. The most common abnormalities included either UPD or copy number loss of chromosome 3q21.2–q21.31, which was identified in 6 (21%) patients. This region harbors CD86, the gene encoding the B7.2 protein responsible for T cell activation and regulation through costimulatory mechanisms. Copy number loss/UPD was also identified at chromosome 1p31.1–p32.3 in 4 (18%) patients. Interestingly, copy number gain in this same region was identified in 2 (9%) patients suggesting that this region may correspond to either a new, infrequent germ line encoded CNV or represents a somatic microdeletion. Recent studies indicated a role for SIL/SCL, which resides at this locus, in V(D)J recombination, lymphocyte development, and maturation. Additional conserved chromosomal abnormalities included copy number gains in 14q (11%) and copy number loss at 11p15 (14%), all possibly representing germ line or somatic CNV physiologically acquired during lymphocyte ontogenesis. We compared chromosomal lesions identified in our LGL cohort with clinical features including age, presence of neutropenia, anemia, thrombocytopenia, splenomegaly, immunophenotype, and degree of clonal expansion. No difference in clinical course was found between patients with and without cytogenetic abnormalities with regard to type and severity of cytopenias or size of the LGL clone. However, patients with 1p31.1–p32.3 deletions were found to have lesser degree of neutropenia compared to patients without 1p31.1–p32.3 deletions (p<0.001). While these data may reflect chromosomal variants and random somatic abnormalities, the recurrent loss of heterozygosity and gains within several loci with known regulatory function for lymphocyte biology suggests the involvement of these defects in the mechanism of clonal evolution.

Autoproliferation Contributes to Clonal Expansion and Changes In Cellular Topography In T Cell Large Granular Lymphocyte (LGL) Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1373-1373
Author(s):  
JianXiang Zou ◽  
Jeffrey S Painter ◽  
Fanqi Bai ◽  
Lubomir Sokol ◽  
Thomas P. Loughran ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Cd8 T Cell ◽  
Effector Memory ◽  
Ki67 Expression ◽  
Terminal Effector ◽  
Lgl Leukemia

Abstract Abstract 1373 Introduction: LGL leukemia is associated with cytopenias and expansion of clonally-derived mature cytotoxic CD8+ lymphocytes. The etiology of LGL leukemia is currently unknown, however, T cell activation, loss of lymph node homing receptor L-selectin (CD62L), and increased accumulation of T cells in the bone marrow may lead to suppressed blood cell production. The broad resistance to Fas (CD95) apoptotic signals has lead to the hypothesis that amplification of clonal cells occurs through apoptosis resistance. However, the proliferative history has not been carefully studied. To define possible mechanism of LGL leukemia expansion, T cell phenotype, proliferative history, and functional-related surface marker expression were analyzed. Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from 16 LGL leukemia patients that met diagnostic criteria based on the presence of clonal aβ T cells and >300 cells/ml CD3+/CD57+ T cells in the peripheral blood. Samples were obtained from 10 age-matched healthy individuals from the Southwest Florida Blood Services for comparisons. Multi-analyte flow cytometry was conducted for expression of CD3, CD4/8, CD45RA, CD62L, CD27, CD28, CD25, CD127, IL15Ra, IL21a, CCR7 (all antibodies from BD Biosciences). The proliferative index was determined by Ki67 expression in fixed and permeabilized cells (BD Biosciences) and the proliferative history in vivo was assessed by T-cell-receptor excision circle (TREC) measurement using real-time quantitative PCR (qRT-PCR) in sorted CD4+ and CD8+ T cells. TRECs are episomal fragments generated during TCR gene rearrangements that fail to transfer to daughter cells and thus diminish with each population doubling that reflects the in vivo proliferative history. Results: Compared to healthy controls, significantly fewer CD8+ naïve cells (CD45RA+/CD62L+, 8.4 ± 10.8 vs 24.48 ± 11.99, p=0.003) and higher CD8+ terminal effector memory (TEM) T cells (CD45RA+/CD62L-, 67.74 ± 28.75 vs 39.33 ± 11.32, p=0.007) were observed in the peripheral blood. In contrast, the percentage of CD4+ naïve and memory cells (naïve, central memory, effector memory, and terminal effector memory based on CD45RA and CD62L expression) was similar in patients as compared to controls. The expression of CD27 (31.32 ± 34.64 vs 71.73 ± 20.63, p=0.003) and CD28 (31.38 ± 31.91 vs 70.02 ± 22.93, p=0.002) were lower in CD8+ T cell from patients with LGL leukemia and this reduction predominated within the TEM population (17.63±24.5 vs 70.98±22.5 for CD27, p<0.0001 and 13±20.5 vs 69.43± 21.59 for CD28, p<0.0001). Loss of these markers is consistent with prior antigen activation. There was no difference in CD25 (IL2Ra, p=0.2) expression on CD4+ or CD8+ T cells, but CD127 (IL7Ra, p=0.001), IL15Ra, and IL21Ra (p=0.15) were overexpressed in TEM CD8+ T cell in patients vs controls. All of these cytokine receptors belong to the IL2Rβg-common cytokine receptor superfamily that mediates homeostatic proliferation. In CD8+ T cells in patients, the IL-21Ra was also overexpressed in naïve, central and effector memory T cells. The topography of the expanded CD8+ T cell population was therefore consistent with overexpression of activation markers and proliferation-associated cytokine receptors. Therefore, we next analyzed Ki67 expression and TREC DNA copy number to quantify actively dividing cells and determine the proliferative history, respectively. We found that LGL leukemia patients have more actively dividing CD8+ TEM T cells compared to controls (3.2 ± 3.12 in patients vs 0.44 ± 0.44 in controls, p=0.001). Moreover, the TREC copy number in CD8+ T cells was statistically higher in healthy individuals after adjusting for age (177.54 ± 232 in patients vs 1015 ± 951 in controls, p=0.019). These results show that CD8+ cells in the peripheral compartment have undergone more population doublings in vivo compared to healthy donors. In contrast, the TREC copies in CD4+ T-cells were similar between LGL patients and controls (534.4 ± 644 in patients vs 348.78 ± 248.16 in controls, p>0.05) demonstrating selective cellular proliferation within the CD8 compartment. Conclusions: CD8+ T- cells are undergoing robust cellular activation, contraction in repertoire diversity, and enhanced endogenous proliferation in patients with LGL leukemia. Collectively, these results suggest that clonal expansion is at least partially mediated through autoproliferation in T-LGL leukemia. Disclosures: No relevant conflicts of interest to declare.

The large granular lymphocytic leukemia registry: A detailed analysis of 79 patients with LGL leukemia and rheumatoid arthritis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6590-6590
Author(s):  
Kirsten Marie Boughan ◽  
Thomas P. Loughran
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Marrow ◽  
T Cell ◽  
T Cell Receptor ◽  
Gene Rearrangement ◽  
Receptor Gene ◽  
Cell Receptor ◽  
T Cell Receptor Gene ◽  
Lgl Leukemia ◽  
Cell Receptor Gene

6590 Background: The purpose of this study is to analyze patients enrolled in the LGL leukemia registry to distinguish the similarities between LGL leukemia and rheumatoid arthritis in order to access overlapping immune mechanisms that may be responsible for neutrophil mediated destruction. Methods: A retrospective chart review was performed on 79 patients enrolled in the LGL registry at Penn State Cancer Institute. All patients enrolled in the study had a diagnosis of both rheumatoid arthritis and potentially LGL leukemia. Data was collected for age, sex, RF factor positivity, family history, autoimmune disease, T-cell receptor gene rearrangement, and bone marrow invasion. Results: Of 79 patients the mean age of onset for LGL leukemia was 60 years old with no discrepancy noted between sexes, 37 M, 42 F. 49 patients were positive for rheumatoid factor. 27 patients had rheumatoid arthritis in a first degree relative with no discrimination between maternal or paternal inheritance. 22 patients were positive for any other autoimmune process. 60 patients were positive for T-cell receptor gene rearrangement. Of the remaining 19 patients that were negative for T-cell receptor rearrangement, 12 had evidence of bone marrow invasion (CD3/CD8+ infiltrate in >20% bone marrow) and two showed bone marrow invasion of NK cell LGL (CD3/CD8-, CD57+) (Table). Conclusions: Patients with T cell LGL leukemia and rheumatoid arthritis appear to be clinically similar with regard to age, duration of disease, and other autoimmune disorders as patients with rheumatoid arthritis alone. Our patient population showed those with TLGL and RA also tends to have a positive family history of RA in up to 20% as opposed to 5-10% in RA patients. Given that RA and TLGL have a significantly higher expression of the HLA-DR4 haplotype than healthy patients, it is conceivable that with shared genetic alterations, and gene environment interactions that may promote posttranslational modification, there may be a loss of tolerance resulting in T cell activation, and eventual transformation into a T cell clone. [Table: see text]

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