t(8;14)(q11;q32) IGH/CEBPD

2008-05-01   Jean-Loup Huret 

1.Genetics, Dept Medical Information, University of Poitiers; CHU Poitiers Hospital, F-86021 Poitiers, France

Clinics and Pathology

Disease

CD10+ acute lymphoblastic leukemia (ALL) in most cases; chronic myelogenous leukemia (CML) very rarely; one case of histiocyte-rich B-cell lymphoma.

Etiology

Strikingly, more than 1/4 of cases are Down syndrome patients.

Epidemiology

At least 52 cases to date (see Ref. below); the t(8;14)(q11;q32) represents about 1/1 000 cases of childhood leukemias; median age is 11 yrs (range 3-49), with 10% above 20 yrs; unbalanced sex ratio (29M/18F).

Clinics

Organomegaly is not frequent, central nervous system (CNS) involvement was not noted; WBC was < 50 X 109/l in most cases.
Atlas Image

Prognosis

Prognosis is likely to be not bad, although a long follow up is missing in about half of the cases (see Figure 2).

Cytogenetics

Cytogenetics morphological

Sole (acquired) anomaly in 1/3 of cases; accompany a t(9;22)(q34;q11) in 20% of cases; unbalanced form with a der(14) t(8;14) in 15% of cases, indicating that the crucial event is likely to lie on der(14). One case was a three way translocation t(2;14;8).

Additional anomalies

t(8;14) may be found with t(9;22) (see above); t(8;14) is accompanied by an acquired (not constitutional) +21 in 10% of cases; +X, +8, and del(13q) are also recurrently found with t(8;14).

Genes Involved and Proteins

Gene name
CEBPD (CCAAT/enhancer binding protein delta)
Location
8q11.21
Protein description
DNA-binding protein. CCAAT enhancer-binding protein (CEBP) transcription factors are a family of 6 multifunctional basic leucine zipper (bZIP) transcription factors. The 5 other CEBPs are: CEBPA (19q13), CEBPB (20q13), CEBPE (14q11), CEBPG (19q13), all four 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. CEBPD is composed of a N-term transactivation domain, a DNA-binding basic motif, and a leucine-zipper domain in C-term (Ramji et al., 2002; Nerlov et al., 2007).
Gene name
IGH (Immunoglobulin Heavy)
Location
14q32.33

Result of the Chromosomal Anomaly

Oncogenesis

Overexpression of the CEBP gene.

Bibliography

Pubmed IDLast YearTitleAuthors
171701242007Five members of the CEBP transcription factor family are targeted by recurrent IGH translocations in B-cell precursor acute lymphoblastic leukemia (BCP-ALL).Akasaka T et al
109149382000Cytogenetic and FISH studies of a single center consecutive series of 152 childhood acute lymphoblastic leukemias.Andreasson P et al
114805762001Three further cases of t(8;14)(q11.2;q32) in acute lymphoblastic leukemia.Byatt SA et al
34930411987Lack of association between abnormalities of the chromosome 9 short arm and either "lymphomatous" features or T cell phenotype in childhood acute lymphocytic leukemia.Carroll AJ et al
23789821990Philadelphia chromosome positive childhood acute lymphoblastic leukemia: clinical and cytogenetic characteristics and treatment outcome. A Pediatric Oncology Group study.Crist W et al
98582101998Bone marrow transplantation for adults with acute leukaemia and 11q23 chromosomal abnormalities.Forrest DL et al
2364166199014q32 translocations are associated with mixed-lineage expression in childhood acute leukemia.Hayashi Y et al
10580431975Chromosomes and causation of human cancer and leukemia. XVI. Banding studies of chronic myelocytic leukemia, including five unusual Ph11 translocations.Hayata I et al
110784972000Abnormalities of chromosome bands 13q12 to 13q14 in childhood acute lymphoblastic leukemia.Heerema NA et al
21252571990Cytogenetic analysis of 51 patients with chronic myeloid leukemia.Hu N et al
106737392000Acute lymphoblastic leukemia with an unusual t(8;14)(q11.2;q32): a Pediatric Oncology Group Study.Kaleem Z et al
69564381982Childhood acute lymphoblastic leukemia associated with an unusual 8;14 translocation.Kardon NB et al
86309901996Down syndrome, acute lymphoblastic leukemia, and t(8;14)(q11;q32)Lee AC et al
76587081995Acute leukemia and the transient myeloproliferative disorder associated with Down syndrome: morphologic, immunophenotypic and cytogenetic manifestations.Litz CE et al
112370732001Multicolor spectral karyotyping identifies novel translocations in childhood acute lymphoblastic leukemia.Mathew S et al
125818912003Acute lymphoblastic leukemia characterized by t(8;14)(q11.2;q32).Moore S et al
176582612007The C/EBP family of transcription factors: a paradigm for interaction between gene expression and proliferation control.Nerlov C et al
15715501992Isochromosomes in childhood acute lymphoblastic leukemia: a collaborative study of 83 cases.Pui CH et al
83154341993Immunophenotypes and karyotypes of leukemic cells in children with Down syndrome and acute lymphoblastic leukemia.Pui CH et al
120061032002CCAAT/enhancer-binding proteins: structure, function and regulation.Ramji DP et al
8580796199517p anomalies in lymphoid malignancies: diagnostic and prognostic implications.Schoch C et al
82425991993Two Down syndrome patients with an acquired translocation, t(8;14)(q11;q32), in early B-lineage acute lymphoblastic leukemia.Secker-Walker LM et al
82591051994Neurofibromatosis type I and malignancy: review of 32 pediatric cases treated at a single institution.Shearer P et al
93859441997Histiocyte-rich B-cell lymphoma.Sun T et al
85044001993t(8;14)(q11;q32) in acute lymphoid leukemia: description of two cases.Testoni N et al
99220411998Accumulation of methotrexate polyglutamates, ploidy and trisomies of both chromosomes 4 and 10 in lymphoblasts from children with B-progenitor cell acute lymphoblastic leukemia: a Pediatric Oncology Group Study.Whitehead VM et al
19975331991Chromosomes in childhood acute lymphoblastic leukaemia: karyotypic patterns in disease subtypes.Wodzinski MA et al

Summary

Fusion gene

IGH/CEBPD IGH (14q32.33) CEBPD (8q11.21) M t(8;14)(q11;q32)
Atlas Image
- 8, + der(14) t(8;14)(q11;q32) G banding (left) - Courtesy Gitte Birk Kerndrup and Steen Rosthoj; der(14) t(8;14)(q11;q32) R-banding - Courtesy Pascale Cornillet-Lefebvre and Stephanie Struski (top), and with a constitutional trisomy 21 (bottom) - Courtesy Petr Balicek, Jana Rabasova, and Jiri Hak. More iconography can be found in the Case Report section (see below).

Citation

Jean-Loup Huret

t(8;14)(q11;q32) IGH/CEBPD

Atlas Genet Cytogenet Oncol Haematol. 2008-05-01

Online version: http://atlasgeneticsoncology.org/haematological/1112/t(8;14)(q11;q32)-igh-cebpd

Historical Card

2005-05-01 t(8;14)(q11;q32) IGH/CEBPD by  Jean-Loup Huret 

Genetics, Dept Medical Information, University of Poitiers; CHU Poitiers Hospital, F-86021 Poitiers, France

1999-11-01 t(8;14)(q11;q32) IGH/CEBPD by  Jean-Loup Huret 

Genetics, Dept Medical Information, University of Poitiers; CHU Poitiers Hospital, F-86021 Poitiers, France

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