Academic Haematology and Cytogenetics, Royal Marsden Hospital/Institute of Cancer Research London UK.
February 2001
Summary: T-cell lymphoid disorders include a variety of disease entities which result from the clonal neoplastic expansion of an uncommitted (thymic) or a committed (post thymic) T-cell. Some of these diseases have distinct cytogenetic/molecular genetic features which allow to better define the various entities and understand their pathogenesis.
Disease entity | Immunophenotype/ Functional activity | Cytogenetics | Molecular genetics | Disease Features. |
T-prolymphocytic leukemia(T-PLL) Variants:small cell and cerebriform cell | TdT-,CD1a-, CD4+ CD8- CD4 - CD8+ CD4+ CD8+
|
Inv(14)(q11q32) t(14;14)(q11; q32) Xq28 abnorm. idic(8)(p11) t(8; 8)(p11;q1-2) 11q22-23 abnorm. 12p abnorm 13q14.3 deletions | ATMgene (11q22-23) mutated. TCL1 (14q32.1) or MTCP1(Xq28) activated | Aggressive course splenomegaly, high WBC with prolymphocytes |
Large granular lymphocyte leukemia(LGL) a.T-cell Type
b.NK type
|
TdT-,CD1a
CD3+,CD2+,CD8+ CD4 -,CD57+, CD16+/- Cytotoxic or suppressor activity
CD2+,CD56+, CD16+ ,CD7+/- CD3-, CD5-,TCR- Natural killer Activity. | Clonal abnormalities.in some cases,but no consistent specific abnormalities
del(6)(q21-25) | Clonality established by TCR rearrangements
TCR chain genes in germ line.
| Indolent, cytopenias, splenomegaly, lymphocytosis with granular lymphocytes
Aggressive or indolent lymphocytosis Splenomegaly hepatomegaly |
Sezary syndrome (SS)
| TdT-, CD1a-, CD3+,CD4+,CD8- Helper or no functional activity | Complex,clonal,oligoclonal or nonclonal with variable ploidy Abnorm.2p,6q i(17q),del 13q14 | P53 gene deletion and protein expression in the absence of gene mutation. Few cases express MDM2 | Variable clinical course with skin involvement and cells with cerebriform nuclei |
Adult T-cell leukemia lymphoma (ATLL )
| TdT-,CD1a-CD7-CD4+CD8-CD25+ Suppressor activity | Complex and often oligoclonal. Numerical abnorm;3,7,X Structural abnorm.1q,3q 6q,14q. | Oligoclonal/mono clonal integration of HTLV-1in host DNA Abnormalities of p53, p16 and p15 genes. | Aggressive , hypercalcaemia Lymph - adenopathy, flower cells, HTLV-1 Positive. |
a/d T-NHL hepatosplenic lymphoma
| TdT- CD1a-CD3+/- CD56+, CD7+,granzymeA+,TCR g/d+ | Abnorm.7q, i (7p) | TCR genes gamma/delta Rearranged but alpha/beta not rearranged | Aggressive, Hepato splenomegaly |
Peripheral/post-thymic T cell lymphoma (pleomorphic and immunoblastic subtypes ) | TdT-,CD1a- Variable expression of CD4 or CD8 | variable | Aggressive Advanced stages . | |
Angio immunoblastic T-cell lymphoma
|
TdT-,CD1a-, CD2+, CD5+,CD3+ CD4+ CD8- | Complex with multiple related or unrelated clones.+3 or i(3q),+5, del(6)(q). Progression from normal karyotype to abnormal clone observed during transition from hyperplasia to neoplasia. | Integrated EBV sequences present in both B-and T-cells and is unlikely to be the etiological agent. | Disproteinemia lymphadenopathy,immune abnormalities |
Angiocentric (nasal) T-cell lymphoma
|
TdT-,CD1a-,T-cell or NK phenotype . | i(1q), del(6)(q),i(6p) | Majority have no TCR rearrangement EBV clonally integrated and plays a role in the etiology of the disease | Prevalent in Asia and south America Extra nodal involvement. |
Anaplastic (Ki 1+) large cell lymphoma . |
TdT-,CD1a-,CD3+/- CD30+ (Ki 1+),CD15-, CD25+, HLA-Dr+, CD71+. | t(2;5)(p23;q35) | Fusion gene NPM-ALK 2p23 -Nucleolar phosphoprotein-NPM 5q35 -Anaplastic lymphoma kinase-ALK | Aggressive with skin,nodes and extranodal involvement . |
Intestinal T-cell lymphoma
|
TdT CD1a -, CD3+, CD8+, CD103+ CD4-,CD8- | EBV genome present in mexican population but not in the europeans. | Bone pain Coeliac disease, Mesenteric nodes . | |
T-lymphoblastic Lymphoma/leukaemia (T-Lbly/T-ALL )
| TDT+,CD1a+, CD7+, cytCD3+or+/- Other T-cell antigens.Thymic uncommitted T-cell. | del(6)(q21-q22) t (11;14)(p13;q11)t(1;14)(p34;q11) 1p34 : tal-1gene 14q11:TCR alpha chain gene | TCR chain genes rearranged .
| Aggressive, mediastinal mass,high WBC,course similar to ALL |
| Bibliography |
| Relationship of T leukaemias with cerebriform nuclei to T-prolymphocytic leukaemia: a cytogenetic analysis with in situ hybridization. |
| Brito-Babapulle V, Maljaie SH, Matutes E, Hedges M, Yuille M, Catovsky D |
| British journal of haematology. 1997 ; 96 (4) : 724-732. |
| PMID 9074412 |
| p53 allele deletion and protein accumulation occurs in the absence of p53 gene mutation in T-prolymphocytic leukaemia and Sezary syndrome. |
| Brito-Babapulle V, Hamoudi R, Matutes E, Watson S, Kaczmarek P, Maljaie H, Catovsky D |
| British journal of haematology. 2000 ; 110 (1) : 180-187. |
| PMID 10930996 |
| The D13S25 locus mapping to 13q14.3 locus is deleted in T-Prolymphocytic leukemia |
| Brito-Babapulle V, Baou M, Atkinson S, Catovsky D |
| Int.Natl.J of Hematology. 2000 ; 72 (supplement 1) : page 167. |
| Response to : presence of t(2;5) in primary CD30+ cutaneous lymphoproliferative disorders' |
| DeCocteau JF, Lowsky R, Kinney MC, Kadin ME |
| Blood. 1996 ; 88 : page 3251. |
| Classification of natural killer (NK) cell and NK-like T-cell malignancies. |
| Jaffe ES |
| Blood. 1996 ; 87 (4) : 1207-1210. |
| PMID 8608206 |
| Chromosome abnormalities in adult T-cell leukemia/lymphoma: a karyotype review committee report. |
| Kamada N, Sakurai M, Miyamoto K, Sanada I, Sadamori N, Fukuhara S, Abe S, Shiraishi Y, Abe T, Kaneko Y |
| Cancer research. 1992 ; 52 (6) : 1481-1493. |
| PMID 1540956 |
| Clonal diseases of large granular lymphocytes. |
| Loughran TP Jr |
| Blood. 1993 ; 82 (1) : 1-14. |
| PMID 8324214 |
| CD30-positive large cell lymphomas ('Ki-1 lymphoma') are associated with a chromosomal translocation involving 5q35. |
| Mason DY, Bastard C, Rimokh R, Dastugue N, Huret JL, Kristoffersson U, Magaud JP, Nezelof C, Tilly H, Vannier JP |
| British journal of haematology. 1990 ; 74 (2) : 161-168. |
| PMID 2156548 |
| T-Cell Lymphoproliferative Disorders. Classification, Clinical and Laboratory Aspects |
| Matutes E |
| Advances in Blood Disorders. 2000. |
| Cytogenetic findings in peripheral T-cell lymphomas as a basis for distinguishing low-grade and high-grade lymphomas. |
| Schlegelberger B, Himmler A, Gödde E, Grote W, Feller AC, Lennert K |
| Blood. 1994 ; 83 (2) : 505-511. |
| PMID 8286748 |
| Detection of aberrant clones in nearly all cases of angioimmunoblastic lymphadenopathy with dysproteinemia-type T-cell lymphoma by combined interphase and metaphase cytogenetics. |
| Schlegelberger B, Zhang Y, Weber-Matthiesen K, Grote W |
| Blood. 1994 ; 84 (8) : 2640-2648. |
| PMID 7919378 |
| Consistent presence of isochromosome 7q in hepatosplenic T gamma/delta lymphoma: a new cytogenetic-clinicopathologic entity. |
| Wang CC, Tien HF, Lin MT, Su IJ, Wang CH, Chuang SM, Shen MC, Liu CH |
| Genes, chromosomes & cancer. 1995 ; 12 (3) : 161-164. |
| PMID 7536454 |
| Identification of del(6)(q21q25) as a recurring chromosomal abnormality in putative NK cell lymphoma/leukaemia. |
| Wong KF, Chan JK, Kwong YL |
| British journal of haematology. 1997 ; 98 (4) : 922-926. |
| PMID 9326190 |
| Citation |
| This paper should be referenced as such : |
| Brito-Babapulle V, Matutes E, Catovsky D |
| Classification of T-cell disorder |
| Atlas Genet Cytogenet Oncol Haematol. in press |
| On line version : http://AtlasGeneticsOncology.org/Deep/TcellClassifID20022.htm |
Bibliography
No bibliography items were found for this article.
External Links
Citation
Classification of T-cell disorders
Atlas Genet Cytogenet Oncol Haematol. 2001-02-01
Online version: http://atlasgeneticsoncology.org/deep-insight/20022/classification-of-t-cell-disorders
