Large granular lymphocytic leukaemia with a mixed T-cell/B-cell phenotype.
Akashi K,Shibuya T,Nakamura M,Oogami A,Harada M,Niho Y
British journal of haematology
We report a case of large granular lymphocytic leukaemia (LGLL) with mixed T-cell/B-cell phenotypes. The LGLL cells expressed T-cell markers such as CD1, CD2, CD3, CD5, CD7, CD8 and CD57. The CD8+ LGLL cells coexpressed B-cell markers including CD20 and PCA-1, and a fraction of purified CD8+ LGLL cells secreted double isotypes of immunoglobulins (IgG-kappa and IgA-kappa). Both TCRB and IGH genes were clonally rearranged. The LGLL cells could be divided into at least three subpopulations that were cytogenetically distinct, and all subpopulations involved the 11q23. The expression of both T- and B-cell markers on the LGLL cells suggests the involvement of a putative common lymphoid progenitor in leukaemic transformation.
Acute transformation of chronic large granular lymphocyte leukemia associated with additional chromosome abnormality.
Ohno Y,Amakawa R,Fukuhara S,Huang C R,Kamesaki H,Amano H,Imanaka T,Takahashi Y,Arita Y,Uchiyama T
A patient with large granular lymphocyte (LGL) leukemia that transformed into an acute or aggressive form after 20 months of the chronic phase is reported. The patient's leukemic cells were mature, medium-sized lymphocytes with sparse azurophil granules and the surface phenotypes of the cells were CD2+, CD3-, CD11+, and CD16+. Molecular analysis showed a germ line configuration in both T-cell receptor beta-chain genes and T-cell receptor tau-chain genes. A clonal anomaly of chromosome (trisomy 8) was demonstrated in peripheral blood cells. LGL after acute transformation of the disease displayed large blastic morphology with prominent nucleoli, intense basophilic cytoplasm, and numerous granules. Karyotypic analysis demonstrated a mosaic of trisomy 8 and trisomy 8 with an additional marker chromosome. Thus, transformation of chronic LGL leukemia into an acute or aggressive form in this patient was associated with morphologic and karyotypic changes of the leukemic cells. Patients with a stable form of chronic LGL leukemia should be examined carefully for the possible acute crisis associated with a clonal evolution.
Transformed aggressive γδ-variant T-cell large granular lymphocytic leukemia with acquired copy neutral loss of heterozygosity at 17q11.2q25.3 and additional aberrations.
Zhang Ling,Ramchandren Radhakrishnan,Papenhausen Peter,Loughran Thomas P,Sokol Lubomir
European journal of haematology
T-cell large granular lymphocytic leukemia (T-LGLL) is a rare indolent lymphoproliferative disorder characterized by cytopenias, splenomegaly, and various degrees of T-cell lymphocytosis, due to a clonal expansion of CD8-positive cytotoxic T-cells. Phenotypic variants of T-LGLL include CD4(+) /CD8(-) T-cells, with dual CD4(-) /CD8(-) /γδ(+) T-cells being even rarer. Cytogenetic abnormalities in T-LGLL have rarely been reported, and there is scientific debate regarding the existence of aggressive or transformed variants of T-LGLL. We report a patient with T-LGLL, γδ variant, with nearly 20-year-long duration of cytopenias before transformation to an unusual clinical scenario, manifesting with marked lymphocytosis >100 × 10(9) /L and infiltration of lymph nodes, tonsils, and subcutaneous tissue. Single-nucleotide polymorphism assays revealed acquired copy neutral loss of heterozygosity at 17q and deletion of 3p21.31, in addition to trisomy 5, monosomy X, and monosomy 21. These genetic abnormalities provided a better understanding of the molecular nature and the potentiality of disease transformation.
Differential gene-expression profiling in the leukemia cell lines derived from indolent and aggressive phases of CD56+ T-cell large granular lymphocyte leukemia.
Daibata Masanori,Matsuo Yoshinobu,Machida Hisanori,Taguchi Takahiro,Ohtsuki Yuji,Taguchi Hirokuni
International journal of cancer
As a rule, T cell large granular lymphocyte (T-LGL) leukemia runs a chronic clinical course without need for therapy. Some cases, however, progress to an aggressive disease after the indolent clinical stage. The transformation mechanism into a high-grade malignancy has not been well studied. We have established 2 leukemia cell lines, MOTN-1 and PLT-2, derived from the same clone of CD56+ T-LGL leukemia in chronic and aggressive phases, respectively. The paired availability of such cell lines is valuable in biologic and genetic investigation of T-LGL leukemia. We used a microarray containing 406 cDNAs to elucidate alterations of gene expression between the 2 cell lines. We found a number of genes that were differentially expressed: 13 genes with increased expression and 3 genes with reduced expression in PLT-2 cells as compared to MOTN-1 cells. Increased expression of the dek, rac, Op18, CD6, CD58, CD106, Id2, ATF4, IRF5, ELL2 and D6 genes, and reduced expression of the GzmA and GzmK genes were confirmed by real-time quantitative reverse transcription-PCR, whose results paralleled the microarray data. These upregulated genes encode oncoproteins, cell surface antigens including molecules related to T cell proliferation, transcription factors, and a chemokine receptor. The two downregulated genes encode granzymes that play an important role for induction of cell death. These findings suggest that there is differential gene expression in different clinical phases of T-LGL leukemia and these differentially expressed genes would be potential targets for further studies to identify the genes involved in the transformation process of T-LGL leukemia.
T-cell large granular lymphocyte leukemia transfomation into aggressive T-cell lymphoma: a report of two cases with molecular characterization.
Belhadj Maya,Mansour Dalila,Kaltenbach Sophie,Deau-Fischer Benedicte,Franchi Patricia,Tamburini Jérôme,Chapuis Nicolas,Damotte Diane,Kosmider Olivier,Burroni Barbara,Bouscary Didier
[CD4⁺/CD8⁻ T- cell large granular lymphocytic leukemia: one case report and literatures reviews].
Li Yang,Wu Zhijie,Li Jianping,Li Yuan,Peng Guangxin,Song Lin,Yang Wenrui,Zhou Kang,Zhang Li,Jing Liping,Zhang Fengkui
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi
OBJECTIVE:Presenting the clinical features of one patient with CD4⁺/CD8⁻ T-cell large granular lymphocytic leukemia, to improve the understanding of the disease. METHODS:Clinical data of one patient hospitalized for skin rush and leukocytosis were analyzed, and the related literatures were reviewed. RESULTS:The patient was hospitalized for skin rush and leukocytosis. Routine blood test showed remarkable elevated white blood cell counts and mild anemia. Subsequent hematological examination led to a diagnosis of T- cell large granular lymphocytic leukemia with CD4⁺/CD8⁻ immunophenontype. CONCLUSION:CD3⁺/CD4⁺/CD8⁻ T- cell large granular lymphocytic leukemia is a kind of variant subtype, and is relatively rare, it has different clinical features with classic CD3⁺/CD4⁻/CD8⁺/TCRαβ⁺T- cell large granular lymphocytic leukemia, so differentiating diagnosis is of great importance.
Clinicopathologic, Immunophenotypic, Cytogenetic, and Molecular Features of γδ T-Cell Large Granular Lymphocytic Leukemia: An Analysis of 14 Patients Suggests Biologic Differences With αβ T-Cell Large Granular Lymphocytic Leukemia. [corrected].
Yabe Mariko,Medeiros L Jeffrey,Wang Sa A,Konoplev Sergej,Ok Chi Young,Loghavi Sanam,Lu Gary,Flores Lauren,Khoury Joseph D,Cason R Craig,Young Ken H,Miranda Roberto N
American journal of clinical pathology
OBJECTIVES:T-cell large granular lymphocytic (T-LGL) leukemia is a rare disorder in which the neoplastic cells usually express the αβ T-cell receptor (TCR). To determine the significance of γδ TCR expression in this leukemia, we compared the clinicopathologic, immunophenotypic, and genetic features of patients with T-LGL leukemia expressing γδ TCR or αβ TCR. METHODS:We used the World Health Organization classification criteria to confirm the diagnosis. All patients were diagnosed and treated at our institution. RESULTS:We identified 14 patients with γδ T-LGL leukemia, 11 men and three women; six (43%) patients had a history of rheumatoid arthritis, 10 (71%) had neutropenia, four (29%) had thrombocytopenia, and three (21%) had anemia. Eight (67%) of 12 patients had a CD4-/CD8- phenotype, and four (33%) had a CD4-/CD8+ phenotype. The median overall survival was 62 months. Patients with γδ T-LGL leukemia were more likely to have rheumatoid arthritis (P = .04), lower absolute neutrophil count (P = .04), lower platelet count (P = .004), and a higher frequency of the CD4-/CD8- phenotype (P < .0001). However, there was no significant difference in overall survival between the two groups (P = .64). CONCLUSIONS:Although patients with γδ and αβ T-LGL leukemia show some different clinical or phenotypic features, overall survival is similar, suggesting that γδ TCR expression does not carry prognostic significance.
Mixed-phenotype large granular lymphocytic leukemia: a rare subtype in the large granular lymphocytic leukemia spectrum.
Neff Jadee L,Rangan Aruna,Jevremovic Dragan,Nguyen Phuong L,Chiu April,Go Ronald S,Chen Dong,Morice William G,Shi Min
Large granular lymphocytic leukemia (LGLL) is a chronic proliferation of cytotoxic lymphocytes in which more than 70% of patients develop cytopenia(s) requiring therapy. LGLL includes T-cell LGLL and chronic lymphoproliferative disorder of natural killer (NK) cells. The neoplastic cells in LGLL usually exhibit a single immunophenotype in a patient, with CD8-positive/αβ T-cell type being the most common, followed by NK-cell, γδ T-cell, and CD4-positive/αβ T-cell types. We investigated a total of 220 LGLL cases and identified 12 mixed-phenotype LGLLs (5%): 7 cases with coexistent αβ T-cell and NK-cell clones and 5 with coexistent αβ and γδ T-cell clones. With a median follow-up of 48 months, the clinicopathological characteristics of these patients seemed similar to those of typical LGLL patients. Treatment was instituted in 9 patients, and 5 patients (55%) attained complete hematologic response or partial response. The therapeutic response rate of this cohort is comparable to the reported overall response rate of 40% to 60% in typical LGLL patients. Three patients who did not receive any treatment had progressive or persistent cytopenias. Interestingly, inverted proportions of 2 clones at disease recurrence were identified in 4 patients (36%) and stable clonal proportions in 7 patients (64%). Mixed-phenotype LGLL is rare, and this study underscores the importance of recognizing this rare type of LGLL in patients who may benefit from LGLL treatment.