The complex translocation (9;14;14) involving <i>IGH</i> and <i>CEBPE</i> genes suggests a new subgroup in B-lineage acute lymphoblastic leukemia

Zerrouki, Rachid; Benhassine, Traki; Bensaada, Mustapha; Lauzon, Patricia; Trabzi, Anissa

doi:10.1590/S1415-475738420140368

Acessibilidade / Reportar erro

Brasil

Genetics and Molecular Biology

Español English

Brasil

Español English

sumário « anterior atual seguinte »

Sumário

Human and Medical Genetics • Genet. Mol. Biol. 39 (1) • Jan-Mar 2016 • https://doi.org/10.1590/S1415-475738420140368 copy

The complex translocation (9;14;14) involving IGH and CEBPE genes suggests a new subgroup in B-lineage acute lymphoblastic leukemia

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Many subtypes of acute lymphoblastic leukemia (ALL) are associated with specific chromosomal rearrangements. The complex translocation t(9;14;14), a variant of the translocation (14;14)(q11;q32), is a rare but recurrent chromosomal abnormality involving the immunoglobulin heavy-chain (IGH) and CCAAT enhancer-binding protein (CEBPE) genes in B-lineage ALL (B-ALL) and may represent a new B-ALL subgroup. We report here the case of a 5-year-old girl with B-ALL, positive for CD19, CD38 and HLA-DR. A direct technique and G-banding were used for chromosomal analysis and fluorescentin situ hybridization (FISH) with BAC probes was used to investigate a possible rearrangement of the IGH andCEBPE genes. The karyotype exhibit the chromosomal aberration 46,XX,del(9)(p21),t(14;14)(q11;q32). FISH with dual-color break-apartIGH-specific and CEPBE-specific bacterial artificial chromosome (BAC) probes showed a complex t(9;14;14) associated with a deletion of cyclin-dependent kinase inhibitor 2A (CDKN2A) and paired box gene 5 (PAX5) at 9p21-13 and duplication of the fusion gene IGH-CEBPE.

Keywords
acute lymphoblastic leukemia; CEBPE; FISH; IGH; translocation

Case	Age (yr)/sex	Karyotype	FISH Molecular analysis	Immunophenotype	BM blast cells (%)	WBC x l0⁹/L	References
1	12/M	43,XY,t(14;14)(q11;q32),-2,+3mar,-7,−13,−16, −17,−18,−19,-21,+ring(7 ?),+der(2)t(2;?)(p25;?), +der(17)t(11;17) (q13;pl2	TCR involvement	CD3+, CD7+, CD8+	NA	NA	*Minegishi et al.(1991)*Minegishi M, Tsuchiya S, Minegishi N, Nakamura M, Abo T, Inaba T and Konno T (1991) Functional and molecular characteristics of acute lymphoblastic leukemia cells with a mature T-cell phenotype from a patient with ataxia telangiectasia. Leukemia 5:88-89.
2	Adult/M	45,X,-Y,add(1)(q10),t(1;3)(p12;q25),+i(1)(q10), Add(7) (p22),−10,del(13)(q22q32),inv(14) (q11q32),Add(21)(p11),-22,+mar[27]/46,XY[2]	TCR involvement	CD2+, CD3+, CD4+, CD5+, CD25+	NA	NA	*Haider et al.(2006)*Haider S, Hayakawa K, Itoyama T, Sadamori N, Kurosawa N and Isobe M (2006) TCR variable gene involvement in chromosome inversion between 14q11 and 14q24 in adult T-cell leukemia. J Hum Genet 51:326-334.
3	5.6/F	45,XX,-7,t(14;14)(q11;q32)[14]/46,XX[2]	NA	B lineage	NA	38.7	*Raimondi et al.(2003)*Raimondi SC, Zhou Y, Mathew S, Shurtleff SA, Sandlund JT, Rivera GK, Behm FG and Pui CH (2003) Reassessment of the prognostic significance of hyperdiploidy in pediatric patients with acute lymphoblastic leukemia. Cancer 98:2715-2722.
4	7/F	46,XX,t(14;14)(q11;q32))[13]/46,XX[l]	Breakpoints, were located telomeric, to the TCR andIGH loci	CD10+, CD19+, CD38+	85	171	Shiloh & Cohen (1978)Shiloh Y and Cohen MM (1978) An improved technique of preparing bone-marrow specimens for cytogenetic analysis. In Vitro 14:510-515.
5	36/F	46,XX,del(6)(q32),t(14;14)(q11;q32)[20]	IGH, involvement	CD10+, CD19+, CD22+, CD38+	85	41.1	Liuetal.(2004)Liu S, Bo L, Liu X, Li C, Qin S and Wang J (2004)IGH gene involvement in two cases of acute lymphoblastic leukemia with t(14;14)(q11;q32) identified by sequential R-banding and fluorescence in situ hybridization. Cancer Genet Cyto-genet 152:141-145.
6	44/M	47,XY,t(14;14)(q11;q32),+mar[15]/46,XY[5]	IGH, involvement	CD9+, CD10+, CD19+, CD20+, CD22+, CD38+	92.5	73.6	Liuetal.(2004)Liu S, Bo L, Liu X, Li C, Qin S and Wang J (2004)IGH gene involvement in two cases of acute lymphoblastic leukemia with t(14;14)(q11;q32) identified by sequential R-banding and fluorescence in situ hybridization. Cancer Genet Cyto-genet 152:141-145.
7	45/M	45,XY,dup(5)(q14q21),-7,t(14;14)(q11;q32)[17]	IGH and CEBPE,involvement	CD10+, CD19+, CD34+, CD38+	NA	1	*Akasaka et al.(2007)*Akasaka T, Balasas T, Russell LJ, Sugimoto K-J, Majid A, Walewska R, Karran EL, Brown DG, Cain K, Harder L, et al. (2007) Five members of the CEBP transcription factor family are targeted by recurrent IGH translocations in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Blood 109:3451-3461.
8	39/F	47,XX,+4,t(14;14)(q11;q32)[20]	IGH and CEBPE,involvement	CD10+,CD19+,CD79a+	88.5	3.6	Han et al. (2008)Han Y, Xue Y, Zhang J, Wu Y, Pan J, Wang Y, Shen J, Dai H and Bai S (2008) Translocation (14;14)(q11;q32) with simultaneous involvement of theIGH and CEBPE genes in B-lineage acute lymphoblastic leukemia. Cancer Genet Cytogenet 187:125-129.
9	5/F	46,XX,del(9)(p21),t(9;14;14)(p12;q11;q32)[20]	IGH and CEBPE(PAX5 and CDKN2A, deletion) involvement	CD10+, CD19+, CD22+, CD33+, CD34+, CD38+, CD45+, CD79b+, HLA-DR+	90	3.9	Present case

Sociedade Brasileira de Genética Rua Cap. Adelmio Norberto da Silva, 736, 14025-670 Ribeirão Preto SP Brazil, Tel.: (55 16) 3911-4130 / Fax.: (55 16) 3621-3552 - Ribeirão Preto - SP - Brazil
E-mail: editor@gmb.org.br

Acompanhe os números deste periódico no seu leitor de RSS

[1] Send correspondence to Traki Benhassine. Laboratoire de Biologie Cellulaire et Moléculaire, Faculté des Sciences Biologiques, Université des Sciences et Technologies Houari Boumediene, B.P. 32, 16111 Alger, Algeria. E-mail: trakibenhassine@hotmail.com