| Written | 2009-03 | Elise Labis |
| Laboratory of Medical Genetics, Hospital Jeanne de Flandre, University Hospital Regional Center-CHRU, Avenue Eugène Avinée, 59037 Lille cedex, France |
| Identity |
| ICD-Topo | C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS |
| ICD-Morpho | 9807/3 Mixed phenotype acute leukaemia with t(v;11q23); MLL rearranged |
| ICD-Morpho | 9811/3 B lymphoblastic leukaemia/lymphoma, NOS |
| ICD-Morpho | 9813/3 B lymphoblastic leukaemia/lymphoma with t(v;11q23); MLL rearranged |
| ICD-Morpho | 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS |
| ICD-Morpho | 9920/3 Therapy-related myeloid neoplasms |
| ICD-Morpho | 9989/3 Myelodysplastic syndrome, unclassifiable |
| Atlas_Id | 1120 |
 | |
| t(11;16)(q23;p13.3) G-banding. | |
| Clinics and Pathology |
| Disease | Treatment-related myelodysplastic syndrome (t-MDS) or treatment-related acute leukaemia, usually myeloblastic (t-AML), less often lymphoblastic (t-ALL). Two case reports describe a de novo leukaemia with t(11;16)(q23;p13.3): an AML-M4 (Glassman et al., 2003) and an infant ALL, which switch into AML with retention of the translocation (Stasik et al., 2006). |
| Phenotype / cell stem origin | Variable phenotypes: most often LAM4 in t-AML (but also LAM5a and LAM2); chronic myelomonocytic leukaemia (CMMoL) in t-MDS. |
| Etiology | Chemotherapy for other primary malignancies (including leukaemia, lymphoma and solid tumors) using topoisomerase II inhibitors (epipodophyllotoxins or anthracyclins). |
| Epidemiology | Rare translocation (about twenty cases described), found at any age, from infancy to elder age. |
| Prognosis | Poor, as in other therapy-related leukaemia. |
| Cytogenetics |
| Cytogenetics Morphological | Can be seen with G-banding: chromosome 11 appears shortened, chromosome 16 enlarged (11q- and 16p+). |
| Cytogenetics Molecular | FISH may be needed. |
 | |
| Fish studies using a commercially available MLL break-apart probe (Vysis® LSI® MLL Dual Color). The derivative 11 shows a single green signal indicating rearrangement of the MLL locus. The derivative 16 has the translocated portion of the MLL indicated by a single red signal. | |
| Additional anomalies | In half cases about, no recurrent additional cytogenetic anomalies. |
| Genes involved and Proteins |
| Gene Name | KMT2A (myeloid/lymphoid or mixed lineage leukemia) |
| Location | 11q23.3 |
| Dna / Rna | 37 exons, spanning over 100 kb. |
| Protein | MLL is a "multipartner" gene involved in multiple rearrangements: the most frequent partners are AF4 in 4q21, AF6 in 6q27, AF9 in 9p22, ELL in 19p13.1 and ENL in 19p13.3. MLL is a major regulator of hematopoesis and embryonic development, through HOX genes expression regulation. MLL binds to promotors of HOX genes such as Hoxa7 and Hoxa9 (proteins which regulate hematopoiesis and are normally expressed only in early hematopoietic progenitors) through acetylation and methylation of histones. |
| Gene Name | CREBBP (CREB binding protein) |
| Location | 16p13.3 |
| Dna / Rna | About 154 kb, 32 exons. |
| Protein | It is a transcriptional coactivator involved in coordonating signal from many sequence-specific activators to modulate transcription and/or cell cycle progression. It has endogenous histone acetyltransferase activity and may contribute to transcriptional regulation via targeted acetylation of chromatin. |
| Result of the chromosomal anomaly |
| Transcript | 5' MLL - 3' CBP on the der(11) and 5' CBP - 3' MLL on the der(16). Variable breakpoints: In MLL, almost all of the breakpoints occurs in an 8.3-kb fragment known as the breakpoint cluster region (BCR), encompassing exons 8-14. In CBP, the genomic breakpoints clustered in an 8.2-kb region of intron 3 (BCR 8.2kb), which is different of the breakpoints in CBP for patients with t(8;16) clustered in a 2.3-kb region in intron 2 (BCR 2.3kb). |
| Description | N-Term from MLL (containing the AT-hooks and repression domain) fused to the C-Term of CBP (almost always including the CREB binding domain, bromodomain, histone acetyltransferase domain). |
| Bibliography |
| Translocation (11;16)(q23;p13) acute myelogenous leukemia and myelodysplastic syndrome. |
| Glassman AB, Hayes KJ. |
| Ann Clin Lab Sci. 2003 Summer;33(3):285-8. |
| PMID 12956443 |
| All patients with the t(11;16)(q23;p13.3) that involves MLL and CBP have treatment-related hematologic disorders. |
| Rowley JD, Reshmi S, Sobulo O, Musvee T, Anastasi J, Raimondi S, Schneider NR, Barredo JC, Cantu ES, Schlegelberger B, Behm F, Doggett NA, Borrow J, Zeleznik-Le N. |
| Blood. 1997 Jul 15;90(2):535-41. |
| PMID 9226152 |
| Infant acute lymphoblastic leukemia with t(11;16)(q23;p13.3) and lineage switch into acute monoblastic leukemia. |
| Stasik C, Ganguly S, Cunningham MT, Hagemeister S, Persons DL. |
| Cancer Genet Cytogenet. 2006 Jul 15;168(2):146-9. |
| PMID 16843104 |
| Characterization of genomic breakpoints in MLL and CBP in leukemia patients with t(11;16). |
| Zhang Y, Zeleznik-Le N, Emmanuel N, Jayathilaka N, Chen J, Strissel P, Strick R, Li L, Neilly MB, Taki T, Hayashi Y, Kaneko Y, Schlegelberger B, Rowley JD. |
| Genes Chromosomes Cancer. 2004 Nov;41(3):257-65. |
| PMID 15334549 |
| Citation |
| This paper should be referenced as such : |
| Huret, JL |
| t(11;16)(q23;p13) |
| Atlas Genet Cytogenet Oncol Haematol. 1998;2(2):60-61. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Anomalies/t1116q23p13ID1120.html |
| Other genes implicated (Data extracted from papers in the Atlas) [ 2 ] |
| Genes | CREBBP | KMT2A |
| Translocations implicated (Data extracted from papers in the Atlas) |
| t(11;16)(q23;p13.3) KMT2A/CREBBP | |
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year articles | automatic search in PubMed |
| All articles | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Mon Sep 7 15:08:08 CEST 2020 |
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