Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

dup (11q) in myeloid malignancies

Written2016-11Adriana Zamecnikova, Soad Al Bahar
/ Kuwait Cancer Control Center, Department of Hematology, Laboratory of Cancer Genetics, Kuwait

Abstract Partial gain of the long arm of chromosome 11, containing the unrearranged mixed lineage leukaemia (MLL) gene (KMT2A; lysine (K)-specific methyltransferase 2A) is a rare but recurrent anomaly in myeloid malignancies, and is often associated with an older age and a higly complex karyotype.

(Note : for Links provided by Atlas : click)


ICD-Topo C420,C421,C424
ICD-Morpho 9920/3 Therapy-related myeloid neoplasms
ICD-Morpho 9980/3 Refractory anemia
ICD-Morpho 9983/3 Refractory anaemia with excess blasts
ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
ICD-Morpho 9873/3 AML without maturation
ICD-Morpho 9874/3 AML with maturation
ICD-Morpho 9867/3 Acute myelomonocytic leukaemia
ICD-Morpho 9891/3 Acute monoblastic and monocytic leukaemia
ICD-Morpho 9910/3 Acute megakaryoblastic leukaemia
ICD-Morpho 9975/3 Chronic myelogenous leukaemia, BCR-ABL1 positive; Myeloproliferative neoplasm, unclassifiable; Myelodysplastic/myeloproliferative neoplasm, unclassifiable
Atlas_Id 1629
Note A different mode of duplication is the internal partial tandem duplication (PTD) of KMT2A (MLL) (MLL-PTD), repeating the 5' part of the gene leading to its self-fusion. MLL-PTD occurs in approximately 10% of cytogenetically normal acute myeloid leukemias (AML) and in the majority of AML cases with trisomy 11 as a sole abnormality.
  (A) Partial karyotypes with 11q duplication. (B) Fluorescence in situ hybridization (FISH) with LSI MLL (Vysis/Abott, USA) showing intrachromosomal duplication of MLL (KMT2A) (2 fusion signals on 11q+) on metaphase and interphase cells.

Clinics and Pathology

Disease Chronic myeloproliferative neoplasms and acute myeloid leukemia (AML).
Phenotype / cell stem origin Phenotype / cell stem origin 25 of the 29 cases presented were AML, 3 were diagnosed with myelodysplasia (MDS) (Werner et al., 1992; Harrison et al., 1998; MacGrogan et al., 2004) and 1 with chronic myeloid leukemia (CML) (Pedersen et al., 2000). While the most common phenotype of AML cases with MLL translocations is AML-M4/M5, the phenotype of AML cases was AML-M1 (7 patients) mainly (Soni et al., 1996; Green et al.,1999; Cuthbert et al., 2000; Brezinova et al., 2002; Mrozek et al., 2002; Arnaud et al., 2005; Babicka et al., 2007). In addition, there were 1 AML-M0 (Van Limbergen et al., 2002), 5 AML-M2 (Soni et al., 1996; Mauritzson et al., 2002; Van Limbergen et al., 2002; Rucker et al., 2006), 1 AML-M4 (Harrison et al., 1998), 4 AML-M5 (Kaneko et al., 1982; Harrison et al., 1998; Xu et al., 2001), 1 AML-M7 (Dastugue et al., 2002) and 6 AML not specified cases (Smadja et al., 1989; Lai et al., 1995; Andersen et al., 2005; Babicka et al., 2007; Lessard et al., 2007; Huh et al., 2013). Among the 29 patients, 1 patient developed AML after therapy for multiple myeloma (Soni et al., 1996), 2 after therapy for adenocarcinoma (Mauritzson et al., 2002; Andersen et al., 2005) and 1 after chemotherapy for diffuse large B-cell lymphoma (Huh et al., 2013) (Table 1).
 Sex/ AgeDiagnosisKaryotype
1F/0AML- M551,XX,+1,del(1)(p22)x2,+3,+6,+9,add(10)(p13),dup(11)(q11q21),+19/52,idem,+18
2F/60 AML44,XX,der(1)t(1;4)(q11;p11),+der(1)t(1;7)(p11;p11),-4,del(5)(q14q34),der(7)t(7;17)(q11;q11),dup(11)(q12q13),-12,-17,-20,+mar
4M/53AML44-45,XY,-3,-5,-10,dup(11)(q12q13),add(12)(p12),add(14)(q32),der(17)t(5;17)(p11;p11),i(18)(q10), +1-2mar
5M/59AML-M149-52,XY,+1,+der(2)t(2;11)(q27;q11),der(3)t(3;3)(q23;p23),del(6)(q23),+10, del(11)(q21q23),+dup(11)(q23), +13,add(14)(p13),add(16)(p23),-17,-17,-18,der(19)t(17;19)(q21;p13),inc
6F/83AML- M244-47,XX,-5,der(6)t(6;13)(p22;q21),+der(11)ins(11;11)(q24;q?12q14),+dup(11)(q23q25),+i(11)(q10),del(13)(q?),der(16)t(13;16)(q?;q?13),del(17)(p?),-18, der(22)t(13;22)(q?;p11)
multiple myeloma, chemotherapy
7M/45 AML-M5a46,XX,dup(11)(q23q23)
11 M AML-M1 43,XY,del(5)(q15q33),-7,-11,dup(11)(q13q23),-17,der(18)t(7;18)(q22;q23)/44, idem,+mar
12F/76 AML-M1 45,XX,del(5)(q13q33),del(7)(q?11q36),dup(11)(q23q23),-16,add(16),der(18)t(16;18)(?;p11)
14M/23APL/ AML-M5a46,XY,dup(11)(q?),t(15;17)(q22;q21)
15F/66AML-M146,XX,del(5)(q13q33),dup(11)(q13q23),t(17;20)(q12;q11)/46,XX,del(5),del(7)(q21q31),+8,dup(11)(q23q23), -14,der(17)t(14;17)(q21;q12),der(20)t(17;20)/46,XX,del(5),del(7),+8,der(11)t(11;11)(q23;p?),-14,der(17) t(14;17),der(20)t(17;20)
16M/1 AML-M7 DS 44,XY,t(9;15)(p11;q11),dup(11)(q11q13),-13,-15,-16,der(17)t(16;17)(q11;p11),+21c, der(21)t(13;21)(q21;p11)
17F/61MDS AML-M246,XX,t(6;9)(p11;p11),t(6;13)(p25;q14),ins(17;1)(q25;q21q25),del(19)(q12)/47,idem,+21
46,XX,t(6;9),t(6;13),-13,+mar/46,XX,del(1)(p11p32),-4,-5,add(7)(q31-32),-9, +dup(11)(q13q23),-12,del(14) (q22),-16,-17,ins(17;1),+der(?)t(?;12)(?;q?), +2mar
adenocarcinoma, chemotherapy, radiotherapy
18M/80AML-M144,X,-Y,del(5)(q13q33),der(5)t(5;11)(q35;q13),-7,der(21)t(7;21)(?;q2?1)t(7;21)t(7;21)t(7;21) t(7;21)t(7;21)/ 44,X,-Y,del(5),-7,der(16)t(11;16)(q13;q24),der(21)/44,X,-Y,del(5),-7,dup(11)(q23q25),der(21)
19F/68AML- M243,XX,-4,del(5)(q12q34),der(10)t(1;10)(p13;q26),dup(11)(q?24q?),-17,-18
20M/63AML-M045,XY,der(2)t(2;18)(p13;p11),del(5)(q13q33),der(7)t(7;11),der(11;12)(q10;q10),dup(11)(q?24q?),+13,der(13)t(7;13)(q?;q21)x2,-16,der(17)t(2;17) (p13;q21),der(17)t(7;17)(?;q24), der(18)t(18;20)(q?;p11),der(20)t(7;20)
21M/76AML- M246,XY,der(1;19)t(1;19)(p13;p12)t(1;19)(p36;q13),der(5)t(5;17)(q13;q11-22), dup(11)(q?24q?),der(17)r(5;17) -19,+22,i(22)(q10)x2
22MRAEB44-49,XY,+Y,del(1)(q32),add(2)(p25),del(5)(q15q31),der(6)t(2;6)(q21;q13),del(7)(q22),+9,add(9)(q34)x2, add(11(p13),dup(11)(q13q23),-17,add(17)(p11), add(19)(p13),-20,i(21)(q10),+2mar
23F/86AML 44,XX,dic(5;17)(q11;p11),-7,der(10)t(10;11)(q25;q22)/43,idem,del(3)(p21),dic(4;7)(q11;q11),+7,der(8)t(4;8) (q21;p21),-12,der(12)t(12;21)(p13;q22),der(21)t(12;21)(q?;q21)/43,idem,del(3),dic(4;7),+7,der(8)(4;8),dup(11)(q23q23),-12,der(12)t(12;21),der(21)t(12;21)
adenocarcinoma, chemotherapy
26M/62 AML 45,XY,del(5)(q13q33),del(7)(q22q35),dup(11)(q?),der(17)t(17;21)(p11;?),der(20)t(20;21)(q12;?),-21/ 44,XY, del(4)(q32),del(5),der(7)t(3;7)(q?;q21),-15,der(16)t(15;16)(?;q22),der(17)t(17;21),der(20)t(20;21),-21
27F/66AML-M146,XX,del(5)(q13q33),del(7)(q21q33),dup(11)(q13q23),-17,der(20)t(17;20)(q12;q11)/46,XX,del(5), del(7),+8, dup(11),-14,der(17)t(14;17)(?;q12),der (20)t(17;20)
28M/60AML46,XY,del(5)(q13q33),dup(11)(q23q23)/43,idem,-4,-17,-18/42,idem,del(2)(q21),-6,-dup(11), add(12)(p11), del(12)(p11),-16,-17,-18
29M/63AML42,X,-Y,del(1)(q32),add(2)(q13),-4,add(4)(q31),del(5)(q15q33), add(6)(p25), add(6)(q13),der(7;16)(p10;q10), -8,add(10)(p13),dup(11)(q23q25),add(13)(p11),-16,-17,add(18)(q12),add(20)(q13),+2mar
diffuse large B-cell lymphoma, chemotherapy

Abbreviations: F., female; M., male; AML., acute myeloid leukemia; AML-M5., acute monoblastic leukemia; RAEB., refractory anemia with excess of blasts; AML-M1., acute myeloblastic leukemia without maturation; AML-M2., acute myeloblastic leukemia with maturation; AML-M5a., acute monoblastic leukemia without differentiation; AML-M4., acute myelomonocytic leukemia; AML-M5b., acute monocytic leukemia; RA., refractory anemia; CML., chronic myeloid leukemia; APL., acute promyelocytic leukemia; DS., Down's syndrome; MDS., myelodysplastic syndrome; AML-M0., acute myeloblastic leukemia with minimal differentiation.

Epidemiology 16 male and 13 female patients with median age of 63 years (range 0 to 86 years), among them 2 were infants (aged 0 and 1 years) and a single pediatric case aged 15 years. The ages of the adult patients ranged from 23 to 86 years, with a mean age of 63 years.
Prognosis The over-representation of complex karyotypes in association with unbalanced rearrangements and/or chromosome 5 and 7 anomalies may reflect genomic instability and correlate with an unfavorable outcome in patients with 11q duplications.


Note Fluorescence in situ hybridisation (FISH) allows identification of genes included in the amplified regions such as duplicated copies of MLL located together on the same chromosome arm without gene splitting.
Cytogenetics Morphological Identified as add(11)(q) with cytogenetically heterogeneous breakpoints by conventional cytogenetic analysis. The involved region was within the 11q13 to 25 bands in the majority of patients, clustering within the 11q13 to 23 and 11q23 to 25 regions and within the 11q11 to 21 bands in 4 cases.
Additional anomalies Significantly associated with complex karyotypes; sole anomaly only in 2 patients:1 with refractory anemia with excess of blasts (Werner et al., 1992) and 1 AML case (Harrison et al., 1998), associated with monosomy 10 in 1 (Harrison et al., 1998,), pentasomy 8 in 1 (Harrison et al., 1998) and found in an unrelated clone in 1 AML case (Harrison et al., 1998). Highly complex anomalies in the remaing cases including dicentric chromosomes, highly rearranged chromosome derivatives and unbalanced structural aberrations; loss or deletion of chromosome 5 was found in 10 patients (Smadja et al., 1989; Lai et al., 1995; Soni et al., 1996; Harrison et al., 1998; Mauritzson et al., 2002; Van Limbergen et al., 2002; Van Limbergen et al., 2002; Rucker et al., 2006; Lessard et al., 2007; Huh et al., 2013), while simultaneous loss or deletion of chromosomes 5 and 7 was found in 7 (Green et al.,1999; Cuthbert et al., 2000; Brezinova et al., 2002; Mrozek et al., 2002; MacGrogan et al., 2004; Babicka et al., 2007; Babicka et al., 2007).

Result of the chromosomal anomaly

Fusion Protein
Oncogenesis The MLL gene, located at 11q23, is frequently rearranged in acute leukaemia as either gene fusions or partial tandem duplications, but 11q duplication is a relatively rare anomaly in myeloid malignancies. In the majority of cases it is found as a part of a highly complex karyotype representing clonal evolution that plays a role in disease progression. Chromosome dupplications occurs in a broad spectrum of malignancies and typically leads to inappropriate activation or overexpression of one or more oncogenes located within the amplicon. FISH and expression analyses confirmed MLL as a prominent target within 11q23 copy gain or amplification, providing further evidence for an etiologic role for MLL gain of function in myeloid malignancies. However, as varying and often large parts of 11q are involved in chromosome duplication, it is possibile that gains of other genes such as DDX6, ETS1, and FLI1 may contribute to leukemogenesis as a gain-of-function mutation (Pope et al., 2004).


Centromeric breakage and highly rearranged chromosome derivatives associated with mutations of TP53 are common in therapy-related MDS and AML after therapy with alkylating agents: an M-FISH study
Andersen MK, Christiansen DH, Pedersen-Bjergaard J
Genes Chromosomes Cancer 2005 Apr;42(4):358-71
PMID 15645489
Screening by fluorescence in situ hybridization for MLL status at diagnosis in 239 unselected patients with acute myeloblastic leukemia
Arnaud B, Douet-Guilbert N, Morel F, Le Bris MJ, Herry A, Banzakour S, Bourquard P, Morice P, Le Calvez G, Marion V, Abgrall JF, Berthou C, De Braekeleer M
Cancer Genet Cytogenet 2005 Sep;161(2):110-5
PMID 16102580
Analysis of complex chromosomal rearrangements in adult patients with MDS and AML by multicolor FISH
Babicka L, Ransdorfova S, Brezinova J, Zemanova Z, Sindelarova L, Siskova M, Maaloufova J, Cermak J, Michalova K
Leuk Res 2007 Jan;31(1):39-47
PMID 16687173
Variations in MLL amplification in a patient with acute myeloid leukemia
Brezinová J, Zemanová Z, Cermák J, Kurková S, Sindelárová L, Schwarz J, Michalová K
Leuk Lymphoma 2002 Oct;43(10):2031-5
PMID 12481904
MLL amplification in acute leukaemia: a United Kingdom Cancer Cytogenetics Group (UKCCG) study
Cuthbert G, Thompson K, McCullough S, Watmore A, Dickinson H, Telford N, Mugneret F, Harrison C, Griffiths M, Bown N
Leukemia 2000 Nov;14(11):1885-91
PMID 11069023
Dastugue N, Lafage-Pochitaloff M, Pagès MP, Radford I, Bastard C, Talmant P, Mozziconacci MJ, Léonard C, Bilhou-Nabéra C, Cabrol C, Capodano AM, Cornillet-Lefebvre P, Lessard M, Mugneret F, Pérot C, Taviaux S, Fenneteaux O, Duchayne E, Berger R; Groupe Français d'Hematologie Cellulaire
Cytogenetic profile of childhood and adult megakaryoblastic leukemia (M7): a study of the Groupe Français de Cytogénétique Hématologique (GFCH) Blood
PMID 12091356
Lack of IRF-1 expression in acute promyelocytic leukemia and in a subset of acute myeloid leukemias with del(5)(q31)
Green WB, Slovak ML, Chen IM, Pallavicini M, Hecht JL, Willman CL
Leukemia 1999 Dec;13(12):1960-71
PMID 10602416
Ten novel 11q23 chromosomal partner sites
Harrison CJ, Cuneo A, Clark R, Johansson B, Lafage-Pochitaloff M, Mugneret F, Moorman AV, Secker-Walker LM
European 11q23 Workshop participants Leukemia
PMID 9593286
Therapy-related myeloid neoplasms in 39 Korean patients: a single institution experience
Huh HJ, Lee SH, Yoo KH, Sung KW, Koo HH, Kim K, Jang JH, Jung C, Kim SH, Kim HJ
Ann Lab Med 2013 Mar;33(2):97-104
PMID 23483787
Chromosome pattern in childhood acute nonlymphocytic leukemia (ANLL)
Kaneko Y, Rowley JD, Maurer HS, Variakojis D, Moohr JW
Blood 1982 Aug;60(2):389-99
PMID 6953984
Myelodysplastic syndromes and acute myeloid leukemia with 17p deletion
Lai JL, Preudhomme C, Zandecki M, Flactif M, Vanrumbeke M, Lepelley P, Wattel E, Fenaux P
An entity characterized by specific dysgranulopoïesis and a high incidence of P53 mutations Leukemia
PMID 7885035
Lessard M, Hélias C, Struski S, Perrusson N, Uettwiller F, Mozziconacci MJ, Lafage-Pochitaloff M, Dastugue N, Terré C, Brizard F, Cornillet-Lefebvre P, Mugneret F, Barin C, Herry A, Luquet I, Desangles F, Michaux L, Verellen-Dumoulin C, Perrot C, Van den Akker J, Lespinasse J, Eclache V, Berger R; Groupe Francophone de Cytogénétique Hématologique
Fluorescence in situ hybridization analysis of 110 hematopoietic disorders with chromosome 5 abnormalities: do de novo and therapy-related myelodysplastic syndrome-acute myeloid leukemia actually differ? Cancer Genet Cytogenet 2007 Jul 1;176(1):1-21
PMID 17574959
Structural integrity and expression of the L3MBTL gene in normal and malignant hematopoietic cells
MacGrogan D, Kalakonda N, Alvarez S, Scandura JM, Boccuni P, Johansson B, Nimer SD
Genes Chromosomes Cancer 2004 Nov;41(3):203-13
PMID 15334543
Pooled analysis of clinical and cytogenetic features in treatment-related and de novo adult acute myeloid leukemia and myelodysplastic syndromes based on a consecutive series of 761 patients analyzed 1976-1993 and on 5098 unselected cases reported in the literature 1974-2001
Mauritzson N, Albin M, Rylander L, Billström R, Ahlgren T, Mikoczy Z, Björk J, Strömberg U, Nilsson PG, Mitelman F, Hagmar L, Johansson B
Leukemia 2002 Dec;16(12):2366-78
PMID 12454741
Spectral karyotyping in patients with acute myeloid leukemia and a complex karyotype shows hidden aberrations, including recurrent overrepresentation of 21q, 11q, and 22q
Mrózek K, Heinonen K, Theil KS, Bloomfield CD
Genes Chromosomes Cancer 2002 Jun;34(2):137-53
PMID 11979548
Many unbalanced translocations show duplication of a translocation participant
Pedersen B, Nørgaard JM, Pedersen BB, Clausen N, Rasmussen IH, Thorling K
Clinical and cytogenetic implications in myeloid hematologic malignancies Am J Hematol
PMID 10861810
Expression analyses identify MLL as a prominent target of 11q23 amplification and support an etiologic role for MLL gain of function in myeloid malignancies
Poppe B, Vandesompele J, Schoch C, Lindvall C, Mrozek K, Bloomfield CD, Beverloo HB, Michaux L, Dastugue N, Herens C, Yigit N, De Paepe A, Hagemeijer A, Speleman F
Blood 2004 Jan 1;103(1):229-35
PMID 12946992
Disclosure of candidate genes in acute myeloid leukemia with complex karyotypes using microarray-based molecular characterization
Rücker FG, Bullinger L, Schwaenen C, Lipka DB, Wessendorf S, Fröhling S, Bentz M, Miller S, Scholl C, Schlenk RF, Radlwimmer B, Kestler HA, Pollack JR, Lichter P, Döhner K, Döhner H
J Clin Oncol 2006 Aug 20;24(24):3887-94
PMID 16864856
Refractory anemia with excess of blasts in transformation
Smadja N, Krulik M, de Gramont A, Gonzalez-Canali G, Audebert AA, Debray J
Clinical, hematologic, and cytogenetic findings in nine patients Cancer Genet Cytogenet
PMID 2790747
Clinical and morphological features of cases of trisomy 13 in acute non-lymphocytic leukemia
Soni M, Brody J, Allen SL, Schulman P, Kolitz J, Rai K, Broome JD, Koduru PR
Leukemia 1996 Apr;10(4):619-23
PMID 8618437
Identification of cytogenetic subclasses and recurring chromosomal aberrations in AML and MDS with complex karyotypes using M-FISH
Van Limbergen H, Poppe B, Michaux L, Herens C, Brown J, Noens L, Berneman Z, De Bock R, De Paepe A, Speleman F
Genes Chromosomes Cancer 2002 Jan;33(1):60-72
PMID 11746988
Chromosome analyses in patients with myelodysplastic syndromes: correlation with bone marrow histopathology and prognostic significance
Werner M, Maschek H, Kaloutsi V, Choritz H, Georgii A
Virchows Arch A Pathol Anat Histopathol 1992;421(1):47-52
PMID 1636249
Molecular cytogenetic characterization and clinical relevance of additional, complex and/or variant chromosome abnormalities in acute promyelocytic leukemia
Xu L, Zhao WL, Xiong SM, Su XY, Zhao M, Wang C, Gao YR, Niu C, Cao Q, Gu BW, Zhu YM, Gu J, Hu J, Yan H, Shen ZX, Chen Z, Chen SJ
Leukemia 2001 Sep;15(9):1359-68
PMID 11516096


This paper should be referenced as such :
Zamecnikova A, Al Bahar S
dup (11q) in myeloid malignancies;
Atlas Genet Cytogenet Oncol Haematol. in press
On line version :

External links

arrayMapMorph ( 9920/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapMorph ( 9980/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapMorph ( 9983/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapMorph ( 9861/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapMorph ( 9873/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapMorph ( 9874/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapMorph ( 9867/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapMorph ( 9891/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapMorph ( 9910/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapMorph ( 9975/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
Disease databasedup (11q) in myeloid malignancies
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Sat Jan 21 16:49:08 CET 2017

Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us