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t(14;19)(q32;q13) IGH/CEBPA

Written2004-09Anthony V Moorman, Hazel M Robinson
Leukaemia Research Fund Cytogenetics Group, Cancer Sciences Division, University of Southampton, MP 822, Duthie Building, Southampton General Hospital, Southampton, SO16 6YD, UK
Updated2008-05Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers; CHU Poitiers Hospital, F-86021 Poitiers, France

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
ICD-Morpho 9811/3 B lymphoblastic leukaemia/lymphoma, NOS
Atlas_Id 1335
Note This abnormality is cytogenetically identical but molecularly distinct from the t(14;19)(q32;q13) seen in chronic lymphoid leukaemia (CLL) and other chronic B-cell lymphoproliferative disorders, which results in the juxtaposition of BCL3 with IGH on the der(14) and subsequent over expression of the BCL3 protein.
 
  G-banded metaphase (left) showing the t(14;19)(q32;q13). The derivative chromosomes 14 and 19 are arrowed (bottom) G-banded karyogram showing the t(14;19)(q32;q13) and a add(15q) (top) - Courtesy Anthony V Moorman, Hazel M Robinson; R-banding (right).

Clinics and Pathology

Disease Acute lymphoblastic leukaemia (ALL)
Phenotype / cell stem origin B-lineage immunophenotype and FAB L1, mostly CD10+ : B-cell precursor acute lymphoblastic leukemia (BCP-ALL).
Epidemiology Rare, with only 28 cases reported to date (Heerema et al., 1985; Prigogina et al., 1988; Pui et al., 1993; Andreasson et al., 2000; Robinson et al., 2004; Chapiro et al., 2006; Akasaka et al., 2007). The estimated incidence in childhood and adult ALL is <1%. Among the reported cases there appears to be a female pre-dominance (9M/19F) which is unusual for ALL. The age range of patients is 5 to 76 years with a median of 19 years. This abnormality is most often found in adolescents and young adults.
Clinics Typically, patients with this abnormality have low white cell count of <10 x 109/L, but 10% of patients present with a WBC above 50 x 109/L.
 
Prognosis It is difficult to assess the true prognosis of patients with this abnormality given its rarity, however initial data suggest that the prognosis is better than expected for patients of a similar age (see Figure 2).

Cytogenetics

Note This balanced translocation can usually be identified by G-banding alone. The breakpoint on chromosome 14 is consistently given as 14q32; however the breakpoint on chromosome 19 has, in the past, been more variably attributed, from q11 to q13. It is to be noted, however, that the gene involved on chromosome 19, CEBPA, lies at 38,482,776 bp from pter, very close to the q12 band limit.
Cytogenetics Morphological The t(14;19) has been described as the sole abnormality in 12 out of 28 cases, and is more frequently accompanied by additional structural and/or numerical abnormalities; +21 (acquired) was found in three cases, +6 in two cases. A t(9;22)(q34;q11) was found in one case, a trisomy 8 in one case.
This abnormality has been reported in a single case with Down syndrome. In a closely related translocation, the t(8;14)(q11;q32) with CEBPD/IGH involvement, more than 1/4 of cases were Down syndrome patients.

Genes involved and Proteins

Note The involvement of the IGH gene located at 14q32 has been demonstrated via FISH using the LSI IGH Dual Colour Break Apart Rearrangement Probe in all cases tested. Metaphase and interphase FISH using probes flanking the BCL3 gene have ruled out the involved of this gene; thus distinguishing it from the cytogenetically identical translocation t(14;19)(q32;q13) seen in CLL and other chronic B-cell lymphoproliferative disorders.
Gene NameIGH (Immunoglobulin Heavy)
Location 14q32.33
Gene NameCEBPA (CCAAT/enhancer binding protein (C/EBP), alpha)
Location 19q13.1
Note Alternatively, CEBPG can be involved instead of CEBPA (one case so far described). It is unknown if they bear the same prognosis, as they differ in their N-term.
Dna / Rna CEBPA is a single-exon gene, CEBPG also.
Protein DNA-binding protein. CCAAT enhancer-binding protein (CEBP) transcription factors are a family of 6 multifunctional basic leucine zipper (bZIP) transcription factors. The 4 other CEBPs are: CEBPB (20q13), CEBPD (8q11), CEBPE (8q11), all three equally implicated in leukemias, and DDIT3/CHOP/CEBP zeta (12q13), so far known to be involved in solid tumours (liposarcoma). These transcription factors play a key role in cellular differentiation, in particular in the control of myeloid differentiation. CEBPA is composed of a N-term transactivation domain, a negative regulatory domain, a DNA-binding basic motif, and a leucine-zipper domain in C-term. CEBPA mRNA is translated into two major proteins, p42CEBPA and p30CEBPA. The 30 kDa protein lacks the transactivating domain, and inhibits DNA binding and transactivation by p42CEBPA. CEBPA is essential for the lineage specific differentiation of myelocytic haematopoietic precursors into mature neutrophils. CEBPG only contains a DNA-binding basic motif, and a leucine-zipper domain (Ramji et al., 2002; Nerlov et al., 2007).
Germinal mutations CEBPA has been found mutated in a familial acute myeloid leukemia (Smith et al., 2004).
Somatic mutations 10% of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) cases exhibit a mutation in CEBPA, It seems to bear a good prognosis

Result of the chromosomal anomaly

Fusion Protein
Oncogenesis Overexpression of the CEBP gene.
  

Bibliography

Five members of the CEBP transcription factor family are targeted by recurrent IGH translocations in B-cell precursor acute lymphoblastic leukemia (BCP-ALL).
Akasaka T, Balasas T, Russell LJ, Sugimoto KJ, Majid A, Walewska R, Karran EL, Brown DG, Cain K, Harder L, Gesk S, Martin-Subero JI, Atherton MG, Bruggemann M, Calasanz MJ, Davies T, Haas OA, Hagemeijer A, Kempski H, Lessard M, Lillington DM, Moore S, Nguyen-Khac F, Radford-Weiss I, Schoch C, Struski S, Talley P, Welham MJ, Worley H, Strefford JC, Harrison CJ, Siebert R, Dyer MJ.
Blood. 2007 Apr 15; 109(8): 3451-61. Epub 2006 Dec 14.
PMID 17170124
 
Cytogenetic and FISH studies of a single center consecutive series of 152 childhood acute lymphoblastic leukemias.
Andreasson P, Hoglund M, Bekassy AN, Garwicz S, Heldrup J, Mitelman F, Johansson B
Eur J Haematol. 2000 Jul; 65(1): 40-51.
PMID 10914938
 
Overexpression of CEBPA resulting from the translocation t(14;19)(q32;q13) of human precursor B acute lymphoblastic leukemia.
Chapiro E, Russell L, Radford-Weiss I, Bastard C, Lessard M, Struski S, Cave H, Fert-Ferrer S, Barin C, Maarek O, Della-Valle V, Strefford JC, Berger R, Harrison CJ, Bernard OA, Nguyen-Khac F.
Blood. 2006 Nov 15; 108(10): 3560-3. Epub 2006 Jul 27.
PMID 16873674
 
Karyotypic and clinical findings in a consecutive series of children with acute lymphocytic leukemia.
Heerema NA, Palmer CG, Baehner RL
Cancer genetics and cytogenetics. 1985; 17 (2): 165-179.
PMID 3857967
 
The C/EBP family of transcription factors: a paradigm for interaction between gene expression and proliferation control.
Nerlov C.
Trends Cell Biol. 2007 Jul; 17(7): 318-24. Epub 2007 Jul 19. (Review)
PMID 17658261
 
Nonrandom chromosomal abnormalities in acute lymphoblastic leukemia of childhood.
Prigogina EL, Puchkova GP, Mayakova SA
Cancer genetics and cytogenetics. 1988; 32 (2): 183-203.
PMID 3163259
 
Immunophenotypes and karyotypes of leukemic cells in children with Down syndrome and acute lymphoblastic leukemia.
Pui CH, Raimondi SC, Borowitz MJ, Land VJ, Behm FG, Pullen DJ, Hancock ML, Shuster JJ, Steuber CP, Crist WM
J Clin Oncol. 1993 Jul; 11(7): 1361-7.
PMID 8315434
 
CCAAT/enhancer-binding proteins: structure, function and regulation.
Ramji DP, Foka P.
Biochem J. 2002 Aug 1;365(Pt 3):561-75. (Review)
PMID 12006103
 
t(14;19)(q32;q13): a recurrent translocation in B-cell precursor acute lymphoblastic leukemia.
Robinson HM, Taylor KE, Jalali GR, Cheung KL, Harrison CJ, Moorman AV
Genes, chromosomes & cancer. 2004; 39 (1): 88-92.
PMID 14603446
 
Mutation of CEBPA in familial acute myeloid leukemia.
Smith ML, Cavenagh JD, Lister TA, Fitzgibbon J.
N Engl J Med. 2004 Dec 2; 351(23): 2403-7.
PMID 15575056
 

Citation

This paper should be referenced as such :
Huret, JL
t(14;19)(q32;q13) IGH/CEBPA
Atlas Genet Cytogenet Oncol Haematol. 2009;13(5):378-380.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Anomalies/t1419q32q13ALLID1335.html
History of this paper:
Moorman, AV ; Robinson, HM. t(14;19)(q32;q13) in acute lymphoblastic leukaemia. Atlas Genet Cytogenet Oncol Haematol. 2004;8(4):326-327.
http://documents.irevues.inist.fr/bitstream/handle/2042/38138/09-2004-t1419q32q13ALLID1335.pdf


Other genes implicated (Data extracted from papers in the Atlas) [ 1 ]

Genes CEBPA

Translocations implicated (Data extracted from papers in the Atlas)

 t(14;19)(q32;q13) IGH/CEBPA

External links

IGH (14q32.33) CEBPA (19q13.11)

Mitelman databaset(14;19)(q32;q13) [Case List]    t(14;19)(q32;q13) [Association List] Mitelman database (CGAP - NCBI)
arrayMapTopo ( C42) Morph ( 9811/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
 
Mitelman databaseIGH/CEBPA [MCList]  IGH (14q32.33) CEBPA (19q13.11)
 
Disease databaset(14;19)(q32;q13) IGH/CEBPA
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
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