View source for HAEM4:T-cell lymphoblastic leukemia with t(7;14)(p15;q32)

{{DISPLAYTITLE:T-cell lymphoblastic leukemia with t(7;14)(p15;q32)}}


<blockquote class='blockedit'>{{Box-round|title=PREVIOUS EDITION|This page from the 4th edition of Haematolymphoid Tumours is being updated. See 5th edition [[HAEM5:Table_of_Contents|Table of Contents]].
}}</blockquote>
==Primary Author(s)*==

Rachel Jester
Daynna Wolff

__TOC__

==Cancer Category/Type==

Precursor Lymphoid neoplasms

==Cancer Sub-Classification / Subtype==

T-cell Lymphoblastic leukemia/lymphoblastic lymphoma with t(7;14)(p15;q32)

==Definition / Description of Disease==

T lymphoblastic leukemia/lymphoblastic lymphoma is a neoplasm with clonal proliferation of hematopoietic stem cells committed to the T cell lineage involving either the blood and/or bone marrow (T-ALL) or thymus, nodal, or extra nodal sites (T-LBL). Structural chromosomal abnormalities are detected in approximately 50% of T-ALL/LBL. Other abnormalities include cryptic deletions, often of tumor suppressor genes, and other somatic gene mutations.

Cytogenetic abnormalities of T-ALL/LBL usually involve rearrangements of the T cell receptor (TCR) genes on chromosomes 7 (TCR beta chain: 7q34, gamma chain: 7p14-15) and 14 (alpha/delta chains: 14q11.2) and a variety of non TCR partner genes, often transcription factors juxtaposed to TCR loci promoters and enhancers.

A rare, but recurrent translocation has been seen between chromosome 7p15 and chromosome 14q32. The translocation involves the TCR gamma(γ) gene at 7p15 and either the Immunoglobulin heavy chain (IgH) gene at 14q32. 33 or the TCR-T cell leukemia /Lymphoma 1A (TCLIA) gene at 14q32.13. 


==Synonyms / Terminology==

T-ALL and T-LBL were historically classified separately based on numbers of lymphoblasts in bone marrow, however the current 2008 and incipient 2016 revision of the World Health Organization (WHO) classification of hematopoietic and lymphoid tissues combines these into a single entity: T-ALL/LBL

==Epidemiology / Prevalence==

T-ALL comprises about 15% of childhood and 25% of adult acute lymphoblastic lymphoma with a male predominance. T-LBL comprises approximately 85% of all T-LBL. 
The t(7;14) (p15;q32) is a rare but recurrent cytogenetic abnormality with approximately 12 reported cases to date including a case at out institution for a total of 13 cases. The diagnosis was acute leukemia in all of the cases having this specific translocation. The patients were relatively young with a mean age of 20 and median/mode of 14. The diagnosis was T-ALL/LBL in 11 cases, and AML and pre-B ALL in the remaining two.


==Clinical Features==

T-ALL/LBL usually presents with a high white cell count and circulating blasts and often concurrent mediastinal or other tissue mass. Lymphadenopathy and/or hepatosplenomegaly are common. Pleural effusions, CNS involvement, and relatively spared tri-lineage hematopoiesis in bone marrow may also be seen. T-ALL in children is generally considered higher risk than B-ALL while the opposite is seen in adults. This may be due to the lower prevalence of associated adverse cytogenetic abnormalities in this group. Overall prognosis depends on the patients’ age, LDH level, presenting white blood cell count and extent of disease, and response to initial therapy. 

==Sites of Involvement==

The bone marrow is involved in all cases of T-ALL. T-LBL frequently involves the thymus and may involve nodes or extra nodal sites.

==Morphologic Features==

T-ALL has variable morphology with lymphoblasts on smears ranging from those with high nuclear to cytoplasmic rations and dark condensed chromatin and no nucleoli, to larger blasts with finely dispersed chromatin and prominent nucleoli. Cytoplasmic vacuoles may be present. In bone marrow and on lymph node or thymic hematoxylin and eosin stained sections, the lymphoblasts often efface the normal architecture. Mitotic figures are frequent.  

==Immunophenotype==

Finding 	Marker 
Positive (universal) 	CD45
Positive (subset) 	Cytoplasmic TdT, CD1a, CD34, CD2, CD5, CD7, cytoplasmic CD3 
Negative (universal) 	
Negative (subset) 	CD4, CD8 (in all of the  t(7;14) cases for which data is available)
	


==Chromosomal Rearrangements (Gene Fusions)==

Put your text here and/or fill in the table

{| class="wikitable sortable"
|-
! Chromosomal Rearrangement !! Genes in Fusion (5’ or 3’ Segments) !! Pathogenic Derivative !! Prevalence
|-
|t(7;14)(p14;q32) || 5’TCRγ/3’TCL1A or IGHJ || der(7)  || rare
|-

			
==Characteristic Chromosomal Aberrations / Patterns==

Cytogenetic abnormalities of T-ALL/LBL usually involve rearrangements of the T cell receptor (TCR) genes on chromosomes 7 (TCR beta chain: 7q34, gamma chain: 7p14-15) and 14 (alpha/delta chains: 14q11.2) and a variety of non TCR partner genes, often transcription factors juxtaposed to TCR loci promoters and enhancers.

==Genomic Gain/Loss/LOH==

The data below is from microarray results on a single case and is not necessarily generalizable to all cases with the specific t(7;14)(p15;q32) translocation for which data is unavailable.

{| class="wikitable sortable"
|-
! Chromosome Number !! Gain/Loss/Amp/LOH !! Region
|-
|2q12.2q13  || Loss ||      
|-
|3q26.31q26.32 || Loss || EXAMPLE chr7:0-1000000
|-
|7q35q36.2 || Loss || EXAMPLE chr7:0-1000000
|-
|15q11.2q26.3 || LOH || EXAMPLE chr7:0-1000000
|}		
	

		
==Gene Mutations (SNV/INDEL)==

		
===Other Mutations===


==Epigenomics (Methylation)==



==Genes and Main Pathways Involved==

TCRγ 
Immunoglobulin heavy chain (IgHJ) 
TCR-T cell leukemia /Lymphoma 1A (TCL1A) 


==Diagnostic Testing Methods==

Karyotype.  Fluorescence in situ hybridization (FISH),  PCR for TCR gene rearrangement for clonality testing to show T-cell origin


==Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)==

Given the rarity of this cytogenetic finding, it is difficult to assign prognostic value. Of the known cases, most were relatively young, and, for those on whom data is available, are reported to respond well to therapy and had a generally favorable prognosis. One case of a male over the age of 50 had a poor outcome; however the clinical scenario and other cytogenetic findings are not available. There are no specific therapeutic indications related to t(7;14)(p15q32).

==Familial Forms==

There have been no reported familial forms of T-ALL/LBL with t(7;14)(p15;q32).

==Other Information==

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==Links==

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==References==
<references />
1.	Borowitz M, Chan J. (2008). T lymphoblastic leukemia/lymphoma, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th edition.Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, Editors. IARC Press: Lyon, France, p176-178.

2.	Sugimoto KJ, et al. (2014) T-cell lymphoblastic leukemia/lymphoma with t(7;14)(p15;q32) [TCRγ-TCL1A translocation]: a case report and a review of the literature. Int J Clin Exp Pathol. 2014 Apr 15;7(5):2615-23. eCollection 2014. PMID: 24966976

3.	Larmonie NS et al. (2013) Breakpoint sites disclose the role of the V(D)J recombina¬tion machinery in the formation of T-cell recep¬tor (TCR) and non-TCR associated aberrations in T-cell acute lymphoblastic leukemia. Hae¬matologica; 98: 1173-1184. PMID:23904235

4.	Urbankova H, et al. (2012) Recurrent breakpoints in 14q32.13/TCLA1 region in mature B-cell neoplasms with villous lymphocytes. Leuk Lymphoma. 2012 Dec;53(12):2449-55. PMID: 22553924

5.	Kaneko Y, et al. (1988). Chromosome Translocations involving band 7q35 or 7p15 in childhood T-cell Leukemia/lymphoma. Blood. 1988 Aug;72(2):534-8. PMID:2900030
[[Category:HAEM4]] [[Category:DISEASE]]