| Written | 2016-03 | Jeroen Knijnenburg, H. Berna Beverloo |
| Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands. b.beverloo@erasmusmc.nl |
| This article is an update of : |
| 1997-12 | Jean-Loup Huret | |
| Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France |
| Abstract | Review on t(9;11)(p21;q23), with data on clinics, and the genes involved. |
| Keywords | chromosome 9; chromosome 11; acute myeloid leukemia; KMT2A; MLLT3. |
| Identity |
| ICD-Topo | C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS |
| ICD-Morpho | 9897/3 AML with t(9;11)(p22;q23); MLLT3-MLL |
| ICD-Morpho | 9920/3 Therapy-related myeloid neoplasms |
| Atlas_Id | 1001 |
 | |
| t(9;11)(p21;q23) KMT2A/MLLT3 G- banding (left) - Courtesy Jean-Luc Lai and Alain Vanderhaegen (top 2 rows), Courtesy Diane H Norback, Eric B Johnson, and Sara Morrison-Delap, UW Cytogenetic Services (rows 3 to 6); Courtesy Adriana Zamecnikova (rows 7 and 8); R-banding (right): top: - Courtesy Pascale Cornillet-Lefebvre and Stéphanie Struski, center top: t(9;11)+der(9)t(9;11) - Courtesy Christiane Charrin; bottom 2: - Courtesy Hossein Mossafa. FISH: “Red” chromosomes - Courtesy Pascale Cornillet-Lefebvre and Stéphanie Struski. The probe is MLL; one signal is on the normal 11, one signal on the der(11), and one signal (arrow) on the der(9); pale blue chromosomes - Courtesy Hossein Mossafa (AN: abnormal). (); bottom 3: Hybridization with Kreatech KMT2A/MLLT3 t(9;11) fusion probe (Leica Biosystems, US) showing hybridization on normal (A) and on metaphases with t(9;11) (B,C). - Courtesy Adriana Zamecnikova. | |
| Clinics and Pathology |
| Disease | Acute myeloid leukemia (AML). |
| Phenotype / cell stem origin | Most often found in acute monocytic and myelomonocytic leukaemias, although occasionally also seen in AML with or without maturation (WHO 2008). M5 most often (especially M5a, M4); both found in de novo and therapy related AML with antitopoisomerase II drugs (epipodophyllotoxins, anthracyclins, actinomycin D). Immunophenotype typically shows positivity for CD11, CD13, CD15 and CD33, but less often shows positivity for CD14, CD34 and lymphoid markers. |
| Epidemiology | May occur at any age, but is more common in children, being present in 5-12% of paediatric and 1-2% of adult AML, and equally common in males and females. |
| Clinics | Organomegaly, frequent central nervous system (CNS) involvement, especially in de novo cases; no preceding myelodysplastic phase, unlike classic therapy related AML with chromosome 5 and/or 7 involvement, short interval from initial drug therapy (may even be of 1-2 yrs). Patients may present with disseminated intravascular coagulation and may have tissue infiltration. |
| Cytology | Absence of trilineage dysplasia, unlike classic therapy related AML. |
| Prognosis | Survival is described as poor to intermediate, being superior to AML with other KMT2A translocations. |
| Cytogenetics |
| Cytogenetics Morphological | May easily be overlooked. Previously described as t(9;11)(p22;q23) based on band estimation, but nowadays it is known that MLLT3 is located in 9p21.3 based on molecular positioning. |
| Cytogenetics Molecular | FISH or RT-PCR is indicated in cases with poor chromosome morphology or in cases where the translocation is expected in cases based on morphology, immunophenotype or clinical presentation. |
| Additional anomalies | None in 70% of cases, +8 in 20%, less frequently: additional trisomies of chromosome 6, 19 or 21. |
| Variants | Complex 3 way translocations t(9;11;Var) involving a (variable) third chromosome and insertions have been described, and showed that der(11) is the crucial on |
| Genes involved and Proteins |
| Gene Name | MLLT3 (myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 3) |
| Location | 9p21.3 |
| Protein | Contains a nuclear targeting sequence; transcriptional activator; nuclear localisation. |
| Gene Name | KMT2A (myeloid/lymphoid or mixed lineage leukemia) |
| Location | 11q23.3 |
| Protein | Contains two DNA binding motifs (a AT hook, and Zinc fingers), a DNA methyl transferase motif, a bromodomain; transcriptional regulatory factor; nuclear localisation. |
| Result of the chromosomal anomaly |
| Description | 5' KMT2A- 3' MLLT3; variable breakpoints. |
| Description | N-term -- AT hook and DNA methyltransferase from KMT2A (1444 amino acids) fused to the 192 C-term amino acids from MLLT3 (as breakpoints are variable, this is only an exemple); 180 kDa. |
| Expression Localisation | Nuclear localisation. |
| To be noted |
| You may also have a glance at 11q23 rearrangements, which gives an overview of related diseases. |
| Bibliography |
| Implication of prior treatment with drug combinations including inhibitors of topoisomerase II in therapy-related monocytic leukemia with a 9;11 translocation. |
| Albain KS, Le Beau MM, Ullirsch R, Schumacher H |
| Genes, chromosomes & cancer. 1990 ; 2 (1) : 53-58. |
| PMID 2177642 |
| Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study. |
| Balgobind BV, Raimondi SC, Harbott J, Zimmermann M, Alonzo TA, Auvrignon A, Beverloo HB, Chang M, Creutzig U, Dworzak MN, Forestier E, Gibson B, Hasle H, Harrison CJ, Heerema NA, Kaspers GJ, Leszl A, Litvinko N, Nigro LL, Morimoto A, Perot C, Pieters R, Reinhardt D, Rubnitz JE, Smith FO, Stary J, Stasevich I, Strehl S, Taga T, Tomizawa D, Webb D, Zemanova Z, Zwaan CM, van den Heuvel-Eibrink MM. |
| Blood 2009 ; 114(12):2489-2496. |
| PMID 19528532 |
| Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet |
| Döhner H, Estey EH, Amadori S, Appelbaum FR, Büchner T, Burnett AK, Dombret H, Fenaux P, Grimwade D, Larson RA, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz MA, Sierra J, Tallman MS, Löwenberg B, Bloomfield CD; European LeukemiaNet. |
| Blood. 2010 Jan 21;115(3):453-74. |
| PMID 19880497 |
| Identification of MLL and chimeric MLL gene products involved in 11q23 translocation and possible mechanisms of leukemogenesis by MLL truncation. |
| Joh T, Kagami Y, Yamamoto K, Segawa T, Takizawa J, Takahashi T, Ueda R, Seto M |
| Oncogene. 1996 ; 13 (9) : 1945-1953. |
| PMID 8934541 |
| Translocation t(9;11)(p21;q23) in pediatric de novo and secondary acute myeloblastic leukemia. |
| Sandoval C, Head DR, Mirro J Jr, Behm FG, Ayers GD, Raimondi SC |
| Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1992 ; 6 (6) : 513-519. |
| PMID 1602790 |
| WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues |
| Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW. |
| 4th Edition; Lyon, France: IARC Press; 2008. |
| Citation |
| This paper should be referenced as such : |
| Jeroen Knijnenburg, H Berna Beverloo |
| t(9;11)(p21;q23) KMT2A/MLLT3 |
| Atlas Genet Cytogenet Oncol Haematol. 2016;20(12):613-615. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Anomalies/t0911ID1001.html |
| History of this paper: |
| Huret, JL. t(9;22)(q34;q11) in CML. Atlas Genet Cytogenet Oncol Haematol. 1997;1(2):98-100. |
| http://documents.irevues.inist.fr/bitstream/handle/2042/32071/12-1997-t0911ID1001.pdf |
| Other genes implicated (Data extracted from papers in the Atlas) [ 2 ] |
| Genes | MLLT3 | KMT2A |
| Translocations implicated (Data extracted from papers in the Atlas) |
| t(9;11)(p22;q23) KMT2A/MLLT3 | |
| 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 Dec 14 18:26:14 CET 2020 |
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