| 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. |
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| 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). |
| Gene Name | CEBPA |
| Location | 19q13 |
| 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 |
| 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 |
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| 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 |
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| 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 |
| |
| 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 |
| |
| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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