dup(1)(q11-q44) in myeloid malignancies

2016-06-01   Soad Al Bahar , Adriana Zamecnikova 

1.Kuwait Cancer Control Center, Department of Hematology, Laboratory of Cancer Genetics, Kuwait; annaadria@yahoo.com


Review on dup(1)(q11-q44) in myeloid malignancies, with data on clinics

Clinics and Pathology


Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) and acute myeloid leukemia (AML).

Phenotype stem cell origin

Chronic myeloproliferative disorder in 58 cases and AML in 52 patients.
Chronic myeloproliferative neoplasms: 5 polycythemia vera (PV) (Carbonell et al., 1983; Mamaeva et al., 1983; Rege-Cambrin et al., 1987; Jarosova et al., 1988), 3 essential thrombocythemia (ET) (Knuutila et al., 1983; Richard et al., 1987; Lofvenberg et al., 1990), 10 myelofibrosis (MF) (Schmid and Kohler., 1984; Lawler and Swansbury.,1985; Akahoshi et al., 1987; Fonatsch and Gradl., 1988; Lofvenberg et al., 1990; Andrieux et al., 2003), among them 4 with post-PV myelofibrosis (Andrieux et al 2003) and 2 after therapy for a previous malignancy (Lawler and Swansbury., 1985; Akahoshi et al., 1987). There were 2 chronic myelomonocytic leukemia (CMMoL) (Fonatsch et al., 1991; Trakhtenbrot et al., 2010) cases and 2 patients with unspecified chronic myeloproliferative disorders (Haubenstock et al., 1985; Kerman et al., 1986).
Myelodysplastic syndrome: 25 patients (Anderson and Bagby., 1982; Papenhausen et al., 1984; Yunis et al., 1986; Palmer et al., 1987; Fonatsch et al., 1991; Kanamaru and Tamura., 1993; Ohyashiki et al., 1994; Tien et al., 1994; Satake et al., 1997; Alter et al., 2000; de Souza Fernandez et al., 2000; Kearns et al., 2004; Alfaro et al., 2008; Bacher et al., 2009; Vundinti et al., 2010; Kolquist et al., 2011; Quentin et al., 2011), 8 of them with Fanconi anemia (FA) (Alter et al 2000; Vundinti et al 2010; Quentin et al., 2011).
Chronic myeloid leukemia (CML) was diagnosed in 11 patients (Kohno and Sandberg., 1980; Smadja et al., 1984; Hild and Fonatsch., 1990; Gozzetti et al., 2003; Herens et al., 2003; Lee et al., 2003; Schoch et al., 2003; Abruzzese et al., 2007; Palandri et al., 2009; Sun et al., 2011; Fabarius et al., 2011). In 8 patients dup(1q) was found in association with t(9;22)(q34;q11) (Kohno and Sandberg 1980; Smadja et al., 1984; Hild and Fonatsch., 1990; Lee et al., 2003; Schoch et al., 2003; Palandri et al., 2009; Sun et al., 2011; Fabarius et al., 2011) and it was detected in a Ph-negative clone while on imatinib therapy in 3 patients (Gozzetti et al., 2003; Herens et al., 2003; Abruzzese et al., 2007).
Acute myeloid leukemia: There were 53 patients diagnosed with various forms of AML: 1 AML-M0 (Angelova et al., 2015), 4 AML-M1 (Pui et al., 1990; Tanaka et al., 1997; Taylor et al., 2000; Jekarl et al., 2010), 9 AML-M2 (CG et al., 1988; Tien et al., 1988; Kobayashi et al., 1990; Stuppia et al., 1990; Kudoh et al., 1995; Tamura et al., 1998; Lee et al., 2004; Kim et al., 2009; Beach et al., 2012), 3 AML-M3 (Berger et al., 1988; Cuneo et al 1992; Batzios et al., 2009), 7 AML-M4 (Haas et al., 1985; Misawa et al., 1988; Raynaud et al., 1994; Hda et al., 1996; Forestier et al., 2003; Schmidt et al., 2004; Bao et al., 2006), 5 AML-M5 (Orazi et al., 1988; Soekarman et al., 1992; Harrison et al., 1998; Panagopoulos et al., 2000; Gmidene et al., 2012), 2 AML-M6 (Cuneo et al., 1990; Creutzig et al., 1996), 5 AML-M7 (Shikano et al., 1995; Creutzig et al., 1996; Alvarez et al., 2001; Strehl et al., 2001; Lundin et al., 2012) and 16 AML unspecified cases (Nacheva et al., 1982; Ghaddar et al.,1994; Nacheva et al., 1995; Kolstad et al., 1996; Pallisgaard et al., 1998; Raimondi et al., 1999; Alter et al., 2000; Blann et al., 2000; de Souza Fernandez et al., 2000; Clavio et al., 2001; Seiter et al., 2001; Kern et al., 2002; Oliveira et al., 2002; Quentin et al., 2011). Patients characteristics are reported in Table 1.


At least 110 reported cases in myeloid malignancies (63 males and 47 females, aged 0 to 84 years; median 45 years); male prevalence in chronic myeloid neoplasms (35M/23F, aged 1 to 84 years; median 51 years); balanced sex ratio in AML (28M/24F aged 0 to 72 years; median 33 years). There were 20 pediatric cases (9M/11F;


The prognosis is likely variable in myeloid malignancies as dup(1q) may be present at all stages in the bone marrow, including hypoplastic marrow without morphological evidence of transformation. The appearance of dup(1q) in association with leukaemic or myelofibrotic transformation and/or poor-risk genetic features may be predictive of inferior prognosis (Beach et al., 2012).


Atlas Image
Figure 1. Partial karyotypes showing duplication of the long arm of chromosome 1 (A) and Fluorescence in situ hybridization with LSI 1p36/1q25 probe (Abott, Vysis, USA) showing duplication of 1q25 sequences (green signal) on der(1) chromosome (arrow).

Cytogenetics morphological

Presents as one normal chromosome 1 and a dup(1)(q11-q44) chromosome. The breakpoints in 1q varied from 1q11 to 1q44, with a clustering to 1q21q32 (19 out of 110 cases) and 1q21q42, being duplicated in 13 out of 110 patients.

Additional anomalies

Sole abnormality in 37 patients, mostly in chronic myeloproliferative disorders (3 PV, 3 ET, 6 MF, 1 CMMoL, 14 MDS and 3 CML), and less frequently in AML (7 cases). Associated in combination with an extra chromosome 8 in 11 (Papenhausen et al., 1984;Ohyashiki et al., 1994; Alfaro et al., 2008; Schoch et al., 2003; CG., 1988; Tien et al.,1988; Cuneo et al., 1992; Ghaddar et al., 1994; Creutzig et al., 1996; Tamura et al., 1998; Bao et al., 2006). Loss of chromosome 7 was observed in 3 AML patients (Haas et al., 1985; Hda et al., 1996; Ghaddar et al., 1994) and del(7q) in 4 cases, 3 of them with Fanconi anemia (Alter et al., 2000; Kearns et al., 2004; Quentin et al., 2011). del(5q) was found in 2 AML (Soekarman et al., 1992; Tanaka et al., 1997) and del(20q) was present in 3 (Trakhtenbrot et al., 2010; Kobayashi et al., 1990; Nacheva et al., 1995) cases.
The dup(1q) was apparently secondary anomaly- occurring in a subclone or together with the well-known primary abnormalities such as t(8;21)(q22;q22) in 2 (Tien et al.,1988; Lee et al., 2004), t(9;22)(q34;q11) in 8 CML (Kohno and Sandberg., 1980; Smadja et al., 1984; Hild and Fonatsch 1990; Lee et al., 2003; 54. Schoch et al., 2003; Palandri et al., 2009; Fabarius et al., 2011; Sun et al., 2011) and 1 AML (de Souza et al., 2000). t(15;17)(q24;q21) was found in 2 cases (Berger et al., 1988; Cuneo et al., 1992), 21q22 abnormalities in 5 (Raimondi et al., 1999; Kim et al., 2009; Jekarl et al., 2010) and 11q23 rearrangements in 4 AML patients (Nacheva et al., 1982; Harrison et al., 1998; Taylor et al., 2000; Clavio et al., 2001 ).
Cytogenetic clonal variation with karyotypically unrelated clones was found in 5 MPN (Rege-Cambrin et al., 1987; Andrieux et al., 2003; Alfaro et al., 2008; Hild and Fonatsch 1990; Sun et al., 2011) and 2 AML patients (Alter et al., 2000; Strehl et al., 2001).

Result of the Chromosomal Anomaly


Duplication of all or part of the long arm of chromosome 1 is one of the most frequent chromosomal abnormalities in human neoplasia. In hematologic malignancies of the myeloid lineages, it has been reported in patients with various myeloproliferative conditions, including chronic myeloproliferative neoplasms and acute myelogenous leukemia. Although cytogenetically heterogeneous, duplication of the 1q21-1q32 segment is most commonly observed, indicating that certain chromosome 1 regions might harbor genes that are casually implicated in oncogenesis. The unbalanced nature of this rearrangement indicates, that the sequential duplication of 1q leading to chromosomal imbalances is likely implicated in neoplastic processes by a gene dosage effect. Whether appearance of 1q duplication marks only preleukemic cells participating indirectly, or it may be sufficient as the sole anomaly to promote leukemogenesis is unclear, as well as the role of cytotoxic therapy in some patients.


Pubmed IDLast YearTitleAuthors
175034372007Characterization of Ph-negative abnormal clones emerging during imatinib therapy.Abruzzese E et al
34792281987Myeloproliferative disorders terminating in acute megakaryoblastic leukemia with chromosome 3q26 abnormality.Akahoshi M et al
175096812008dup(1)(q21q32) as a sole cytogenetic event is associated to a leukemic transformation in myelodysplastic syndromes.Alfaro R et al
107046822000Fanconi anemia: myelodysplasia as a predictor of outcome.Alter BP et al
115794692001Frequent gain of chromosome 19 in megakaryoblastic leukemias detected by comparative genomic hybridization.Alvarez S et al
71860851982The prognostic value of chromosome studies in patients with the preleukemic syndrome (hemopoietic dysplasia).Anderson RL et al
146034452004Dysregulation and overexpression of HMGA2 in myelofibrosis with myeloid metaplasia.Andrieux J et al
191005152009Inverted duplication dup(1)(q32q21) as sole aberration in lymphoid and myeloid malignancies.Bacher U et al
165737422006Prospective study of 174 de novo acute myelogenous leukemias according to the WHO classification: subtypes, cytogenetic features and FLT3 mutations.Bao L et al
198066612009Secondary clonal cytogenetic abnormalities following successful treatment of acute promyelocytic leukemia.Batzios C et al
231682432012Duplication of chromosome 1 [dup(1)(q21q32)] as the sole cytogenetic abnormality in a patient previously treated for AML.Beach DF et al
33959831988Cytogenetic studies on acute nonlymphocytic leukemia in relapse.Berger R et al
108121762000Duplication of 1q in a child with down syndrome and myelodysplastic syndrome.Blann MM et al
64040961983Cytogenetic studies in chronic myeloproliferative disorders.Carbonell F et al
114265522001First line therapy with fludarabine combinations in 42 patients with either post myelodysplastic syndrome or therapy related acute myeloid leukaemia.Clavio M et al
88926661996Myelodysplasia and acute myelogenous leukemia in Down's syndrome. A report of 40 children of the AML-BFM Study Group.Creutzig U et al
23867681990Morphologic, immunologic and cytogenetic studies in erythroleukaemia: evidence for multilineage involvement and identification of two distinct cytogenetic-clinicopathological types.Cuneo A et al
31632581988Cytogenetics of acutely transformed chronic myeloproliferative syndromes without a Philadelphia chromosome. A multicenter study of 55 patients. Groupe Français de Cytogénétique Hématologique.
220392532011Impact of additional cytogenetic aberrations at diagnosis on prognosis of CML: long-term observation of 1151 patients from the randomized CML Study IV.Fabarius A et al
79341601994Cytogenetic evolution following the transformation of myelodysplastic syndrome to acute myelogenous leukemia: implications on the overlap between the two diseases.Ghaddar HM et al
225494422012Cytogenetic profile of a large cohort of Tunisian de novo acute myeloid leukemia.Gmidène A et al
129502452003Emergence of Ph negative clones in chronic myeloid leukemia (CML) patients in complete cytogenetic remission after therapy with imatinib mesylate (STI).Gozzetti A et al
95932861998Ten novel 11q23 chromosomal partner sites. European 11q23 Workshop participants.Harrison CJ et al
39381611985Philadelphia-chromosome-negative chronic myelogenous leukemia with incomplete trisomy 1q following chemotherapy for ovarian carcinoma.Haubenstock A et al
86033371996Cytogenetic survey of 53 Moroccan patients with acute myeloblastic leukemia.Hda N et al
145807762003Clonal chromosome aberrations in Philadelphia-negative cells from chronic myelocytic leukemia patients treated with imatinib mesylate: report of two cases.Herens C et al
23576951990Cytogenetic peculiarities in chronic myelogenous leukemia.Hild F et al
33747101988Cytogenetic studies in polycythemia vera.Jarosová M et al
206948422010CD56 antigen expression and hemophagocytosis of leukemic cells in acute myeloid leukemia with t(16;21)(p11;q22).Jekarl DW et al
81242061993Application of long-term bone marrow cultures for studying the leukemic transformation of myelodysplastic syndromes.Kanamaru A et al
151884562004Centrosome amplification and aneuploidy in bone marrow failure patients.Kearns WG et al
34558681986Translocation (1;17) in accelerating and blast phases of chronic myelogenous leukemia.Kerman SL et al
123573612002Karyotype instability between diagnosis and relapse in 117 patients with acute myeloid leukemia: implications for resistance against therapy.Kern W et al
197814432009Detection of FUS-ERG chimeric transcript in two cases of acute myeloid leukemia with t(16;21)(p11.2;q22) with unusual characteristics.Kim J et al
66831221983Chromosome 1q+ in erythroid and granulocyte-monocyte precursors in a patient with essential thrombocythemia.Knuutila S et al
23576931990Karyotypically unrelated clones in acute leukemias and myelodysplastic syndromes.Kobayashi H et al
69329941980Chromosomes and causation of human cancer and leukemia: XXXIX. Usual and unusual findings in Ph1-positive CML.Kohno SI et al
222000862011Microarray-based comparative genomic hybridization of cancer targets reveals novel, recurrent genetic aberrations in the myelodysplastic syndromes.Kolquist KA et al
86856761996Clonal chromosome aberrations in myeloid leukemia after styrene exposure.Kolstad HA et al
23974741990Cytogenetic abnormalities and leukemic transformation in hydroxyurea-treated patients with Philadelphia chromosome negative chronic myeloproliferative disease.Löfvenberg E et al
127599272003A study on the incidence of ABL gene deletion on derivative chromosome 9 in chronic myelogenous leukemia by interphase fluorescence in situ hybridization and its association with disease progression.Lee DS et al
146281542004Adult patients with t(8;21) acute myeloid leukemia had no superior treatment outcome to those without t(8;21): a single institution's experience.Lee KW et al
220724022012High frequency of BTG1 deletions in acute lymphoblastic leukemia in children with down syndrome.Lundin C et al
65732951983Complete or partial trisomy for the long arm of chromosome 1 in patients with various hematologic malignancies.Mamaeva SE et al
31938111988Detection of karyotypic abnormalities in most patients with acute nonlymphocytic leukemia by adding ethidium bromide to short-term cultures.Misawa S et al
69622011982Acute myelogenous leukemia in a child with primary involvement of chromosomes 11 and X.Nacheva E et al
77364431995Characterization of 20q deletions in patients with myeloproliferative disorders or myelodysplastic syndromes.Nacheva E et al
80129811994Telomere shortening associated with disease evolution patterns in myelodysplastic syndromes.Ohyashiki JH et al
123634752002Two different karyotypes with 1q abnormalities in a patient with Fanconi anemia.Oliveira NI et al
31529501988Acute monoblastic leukemia as a second malignancy following chemotherapy for osteogenic sarcoma: a case report.Orazi A et al
191446562009The long-term durability of cytogenetic responses in patients with accelerated phase chronic myeloid leukemia treated with imatinib 600 mg: the GIMEMA CML Working Party experience after a 7-year follow-up.Palandri F et al
96577581998Multiplex reverse transcription-polymerase chain reaction for simultaneous screening of 29 translocations and chromosomal aberrations in acute leukemia.Pallisgaard N et al
35944141987Cytogenetic findings in siblings with a myelodysplastic syndrome.Palmer CG et al
113423502000Acute myeloid leukemia with inv(8)(p11q13).Panagopoulos I et al
67227561984Novel tandem triplication of 1q in a patient with a myelodysplastic syndrome.Papenhausen PR et al
19749521990Myeloid neoplasia in children treated for solid tumours.Pui CH et al
213255962011Myelodysplasia and leukemia of Fanconi anemia are associated with a specific pattern of genomic abnormalities that includes cryptic RUNX1/AML1 lesions.Quentin S et al
105720831999Chromosomal abnormalities in 478 children with acute myeloid leukemia: clinical characteristics and treatment outcome in a cooperative pediatric oncology group study-POG 8821.Raimondi SC et al
83092491994Recurrent cytogenetic abnormalities observed in complete remission of acute myeloid leukemia do not necessarily mark preleukemic cells.Raynaud SD et al
38289701987A chromosomal profile of polycythemia vera.Rege-Cambrin G et al
38020541987Trisomy 1q in a case of essential thrombocythemia with long survival.Richard C et al
92094661997Minimal residual disease in acute monocytic leukemia patient with trisomy 11 and partial tandem duplication of MLL.Satake N et al
65809421984Involvement of chromosomes #1 and #11 in three cases with myeloproliferative diseases.Schmid E et al
150851632004RT-PCR and FISH analysis of acute myeloid leukemia with t(8;16)(p11;p13) and chimeric MOZ and CBP transcripts: breakpoint cluster region and clinical implications.Schmidt HH et al
125923482003Occurrence of additional chromosome aberrations in chronic myeloid leukemia patients treated with imatinib mesylate.Schoch C et al
114174842001Secondary acute myelogenous leukemia and myelodysplasia without abnormalities of chromosome 11q23 following treatment of acute leukemia with topoisomerase II-based chemotherapy.Seiter K et al
76562031995A t(11;14)(p13;q11) specific for T-cell malignancies in acute megakaryoblastic leukemia.Shikano T et al
65946701984[Abnormality of chromosome number 1 in 3 cases of acute transformation of chronic myeloid leukemia].Smadja N et al
16027861992Dek-can rearrangement in translocation (6;9)(p23;q34).Soekarman D et al
111575012001Multiplex reverse transcriptase-polymerase chain reaction screening in childhood acute myeloblastic leukemia.Strehl S et al
22789621990Karyotypic changes identified by HaeIII restriction endonuclease banding in a patient with M2 acute non-lymphoblastic leukemia.Stuppia L et al
213500932011Chromosome 20q deletion: a recurrent cytogenetic abnormality in patients with chronic myelogenous leukemia in remission.Sun J et al
95921831998Cytogenetic analysis of de novo acute myeloid leukemia with trilineage myelodysplasia in comparison with myelodysplastic syndrome evolving to acute myeloid leukemia.Tamura S et al
90029631997Frequent jumping translocations of chromosomal segments involving the ABL oncogene alone or in combination with CD3-MLL genes in secondary leukemias.Tanaka K et al
108537502000Secondary acute myeloblastic leukaemia (AML) (expressing 11q23 mutation) occurring 11 months after chemotherapy/radiotherapy for paediatric non-Hodgkin lymphoma (NHL).Taylor HJ et al
81940461994Cytogenetic studies, ras mutation, and clinical characteristics in primary myelodysplastic syndrome. A study on 68 Chinese patients in Taiwan.Tien HF et al
206555872010Post-essential thrombocythemia myelofibrosis and chronic myelomonocytic leukemia can co-exist with complex cytogenetic abnormalities.Trakhtenbrot L et al
211317522010Incidence of malignancy and clonal chromosomal abnormalities in Fanconi anemia.Vundinti BR et al
37081581986Refined chromosome analysis as an independent prognostic indicator in de novo myelodysplastic syndromes.Yunis JJ et al
29558841987Infants with Down's syndrome. Use of cytogenetic studies and in vitro colony assay for granulocyte progenitor to distinguish acute nonlymphocytic leukemia from a transient myeloproliferative disorder.de Alarcon PA et al
109962022000Chromosomal alterations associated with evolution from myelodysplastic syndrome to acute myeloid leukemia.de Souza Fernandez T et al


Soad Al Bahar ; Adriana Zamecnikova

dup(1)(q11-q44) in myeloid malignancies

Atlas Genet Cytogenet Oncol Haematol. 2016-06-01

Online version: http://atlasgeneticsoncology.org/haematological/1443/dup(1)(q11-q44)-in-myeloid-malignancies