Download Leukaemia Section t(2 14)(p13-16 32)

Atlas of Genetics and Cytogenetics
in Oncology and Haematology
OPEN ACCESS JOURNAL AT INIST-CNRS
Leukaemia Section
Mini Review
t(2;14)(p13-16;q32)
Adriana Zamecnikova
Kuwait Cancer Control Center, Laboratory of Cancer Genetics, Department of Hematology, Shuwaikh,
70653, Kuwait (AZ)
Published in Atlas Database: February 2010
Online updated version : http://AtlasGeneticsOncology.org/Anomalies/t0214p13q32ID1231.html
DOI: 10.4267/2042/44901
This article is an update of :
Huret JL. t(2;14)(p13;q32). Atlas Genet Cytogenet Oncol Haematol 2002;4(6):289.
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2010 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Identity
(A) Partial karyotype showing the t(2;14)(p13;q32) Top - Courtesy Adriana Zamecnikova; Middle and below - Courtesy Melanie Zenger
and Claudia Haferlach. (B) Fluorescence in situ hybridization with LSI IgH/MYC and LSI ALK probe showing the juxtaposition of ALK
(fusion signal) from 2p23 to the region proximal to IgH locus (green signal) on chromosome 14 and translocation of IgH segments to
der(2) chromosome resulting in a green signal on rearranged chromosome 2 - Courtesy Adriana Zamecnikova.
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(11)
1082
t(2;14)(p13-16;q32)
Zamecnikova A
domain between zinc fingers 1 and 2 and an acidic
domain between 3 and 4. 835 amino acids; 91197 Da,
alternative splicing: 6 isoforms, sharing a common Nterminus. Originally named EV19 human homolog
BCL11A; high level of conservation across a wide
range of species; highly homologous to another gene
(BCL11B) on chromosome 14q32.1; like BCL11A,
BCL11B is remarkable in having a large 5' CpG island.
Predominantly expressed in brain and hematopoietic
cells, expression is tightly regulated during B-cell
development; low-level or undetectable BCL11A RNA
expression in most adult tissues. BCL11A is a DNA
sequence-specific transcriptional repressor, an essential
factor in lymphopoiesis, required for B-cell formation
in fetal liver.
Clinics and pathology
Disease
Identified predominantly in B-cell malignancies,
including CLL/SLL, found in 20 cases of chronic
lymphocytic leukemia (CLL), 1 B-prolymphocytic
leukemia, 1 diffuse, mixed small/large cell non
Hodgkin lymphoma (NHL); 8 cases of acute
lymphocytic leukemia (ALL): one T-ALL and 7 BALL (two in association with t(1;19), one in Ph+ ALL,
one with 3-way translocation); two AML (Ph+ M1 and
inv(16)) cases and in one Ph+ CML case.
CLL cases are characterized by marrow involvement,
absolute lymphocytosis, lymphadenopathy, atypical
morphologic features; prolymphocytes may be
increased. Serum lactate dehydrogenase and betamicroglobulin levels are elevated, ZAP70 is expressed.
IgVH genes are unmutaded; most cases are positive for
CD5, CD19 and CD23; weak intensity of
immunoglobuline and CD20, weak or negative CD79b,
CD22, absence of FMC-7.
IgH
Location
14q32
Result of the chromosomal
anomaly
Epidemiology
Fusion protein
Sex ratio: CLL cases 10 males and 6 females patients, 4
unknown; adults: aged 40-68 years, and 3 children aged
6, 10 and 15 years; ALL cases (3 males, 5 females)
were 1 adult 37 years old and 7 children aged 1-17
years; 2 AML cases (1 male, 1 female) were 34 and 45
years old; the CML case was a 21 years old male
patient.
Oncogenesis
Juxtaposition of IgH enhancer elements leading to
inappropriate overexpression of the partner gene
product. BCL11A may be activated through
chromosomal translocation or amplification, leading to
myeloid leukemias in mice and lymphoid malignancies
in humans; the conserved N-terminus of BCL11A.
deregulated expression of BCL11A may play a major
role in the pathogenesis; gains and amplifications of the
region of chromosome 2p13-16 have been reported in
B-cell malignancies, REL, a NF-kappaB gene family
member, mapping within the amplified region is
coamplified with BCL11A in B-NHL cases and HD
lymphoma cell lines; with gains and amplifications,
BCL11A interacts directly with BCL6, that serves a
crucial role in lymphocyte development, also involved
in IG translocations.
The structure of the t(2;14) translocation is a "head-tohead" arrangement, with the breakpoints falling
centromeric to the first exon adjacent to a large CpG
island at the 5' end; BCL11A is deregulated as a
consequence of the translocation, suggesting that
BCL11A may be involved in lymphoid malignancies
through either chromosomal translocation or
amplification.
Prognosis
8 CLL cases were dead after 27-145 months survival;
from available data on 3 ALL cases: they were all dead
(one after 15 months, 2 after bone marrow
transplantation).
Cytogenetics
Cytogenetics morphological
Sole anomaly in 8 documented cases; found in complex
karyotypes; associated with t(14;19)(q32;q13) in 2 CLL
cases, del(6)q in 4 cases, i(9)(q10) in 2 cases, +12 in 3
cases. In two pediatric ALL cases, it was associated
with t(1;19) and in 3 cases it was associated with Ph+
leukemia.
Genes involved and proteins
BCL11A
References
Location
2p16.1
DNA/RNA
Originally assigned to region 1, band 3, 2p13; it has
subsequently been reassigned to 2p16.1.
Protein
BCL11A/EVI9 is a zinc-finger protein, containing 6
Krüppel C2H2 zinc fingers as well as a proline-rich
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(11)
Ueshima Y, Bird ML, Vardiman JW, Rowley JD. A 14;19
translocation in B-cell chronic lymphocytic leukemia: a new
recurring chromosome aberration. Int J Cancer. 1985 Sep
15;36(3):287-90
Nishida K, Taniwaki M, Misawa S, Abe T. Nonrandom
rearrangement of chromosome 14 at band q32.33 in human
lymphoid malignancies with mature B-cell phenotype. Cancer
Res. 1989 Mar 1;49(5):1275-81
1083
t(2;14)(p13-16;q32)
Zamecnikova A
Uckun FM, Gajl-Peczalska KJ, Provisor AJ, Heerema NA.
Immunophenotype-karyotype associations in human acute
lymphoblastic leukemia. Blood. 1989 Jan;73(1):271-80
Sonoki T, Matsuzaki H, Satterwhite E, Nakazawa N, Hata H,
Tucker PW, Taniwaki M, Kuribayashi N, Harada N, Matsuno F,
Mitsuya H. A plasma cell leukemia patient showing bialleic 14q
translocations: t(2;14) and t(11;14). Acta Haematol.
1999;101(4):197-201
Yoffe G, Howard-Peebles PN, Smith RG, Tucker PW,
Buchanan GR. Childhood chronic lymphocytic leukemia with
(2;14) translocation. J Pediatr. 1990 Jan;116(1):114-7
Satterwhite E, Sonoki T, Willis TG, Harder L, Nowak R, Arriola
EL, Liu H, Price HP, Gesk S, Steinemann D, Schlegelberger B,
Oscier DG, Siebert R, Tucker PW, Dyer MJ. The BCL11 gene
family: involvement of BCL11A in lymphoid malignancies.
Blood. 2001 Dec 1;98(12):3413-20
Watson MS, Land VJ, Carroll AJ, Pullen J, Borowitz MJ, Link
MP, Amylon M, Behm FG. t(2;14)(p13;q32): a recurring
abnormality in lymphocytic leukemia. A Pediatric Oncology
Group study. Cancer Genet Cytogenet. 1992 Feb;58(2):121-4
Yin CC, Lin KI, Ketterling RP, Knudson RA, Medeiros LJ,
Barron LL, Huh YO, Luthra R, Keating MJ, Abruzzo LV.
Chronic lymphocytic leukemia With t(2;14)(p16;q32) involves
the BCL11A and IgH genes and is associated with atypical
morphologic features and unmutated IgVH genes. Am J Clin
Pathol. 2009 May;131(5):663-70
Geisler CH, Philip P, Christensen BE, Hou-Jensen K,
Pedersen NT, Jensen OM, Thorling K, Andersen E, Birgens
HS, Drivsholm A, Ellegaard J, Larsen JK, Plesner T, Brown P,
Andersen PK, Hansen MM. In B-cell chronic lymphocytic
leukaemia chromosome 17 abnormalities and not trisomy 12
are the single most important cytogenetic abnormalities for the
prognosis: a cytogenetic and immunophenotypic study of 480
unselected newly diagnosed patients. Leuk Res. 1997 NovDec;21(11-12):1011-23
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(11)
This article should be referenced as such:
Zamecnikova A. t(2;14)(p13-16;q32). Atlas Genet Cytogenet
Oncol Haematol. 2010; 14(11):1082-1084.
1084