Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home   Genes   Leukemias   Solid Tumors   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


Written2018-05Adriana Zamecnikova
Kuwait Cancer Control Center, Kuwait

Abstract Loss of genetic material from the long arm of chromosome 9 is a common finding in patients with hematological malignancies. These deletions can result from true loss of 9q or complex rearrangements such as dicentric chromosomes, unbalanced translocations, and formation of an isochromosome of the short arm of chromosome 9. Isochromosome i(9)(p10) is an infrequent event that has been described mainly in myeloid malignancies and B-cell lymphomas.

Keywords i(9)(p10), JAK2, 9p gain, genomic imbalance.

(Note : for Links provided by Atlas : click)


ICD-Topo C420,C421,C424
ICD-Morpho 9950/3 Polycythaemia vera
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 9920/3 Therapy-related myeloid neoplasms
ICD-Morpho 9705/3 Angioimmunoblastic T-cell lymphoma
ICD-Morpho 9827/3 Adult T-cell leukaemia/lymphoma
ICD-Morpho 9680/3 Diffuse large B-cell lymphoma (DLBCL), NOS; Primary DLBCL of the CNS; Primary cutaneous DLBCL, leg type; EBV positive DLBCL of the elderly; DLBCL associated with chronic inflammation; B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma
ICD-Morpho 9650/3 Classical Hodgkin lymphoma
ICD-Morpho 9699/3 Extranodal marginal zone lymphoma of mucosa- associated lymphoid tissue (MALT lymphoma); Nodal marginal zone lymphoma; Paediatric nodal marginal zone lymphoma
Atlas_Id 1604
  Figure 1. Partial karyotypes with i(9)(p10) (A). Fluorescence in situ hybridization with LSI CDKN2A/CEP9 probe (Vysis/Abott molecular, US) showing 3 copies of CDKN2A located on 9p (red signal) as a result of isochromosome formation (B). Hybridization with whole chromosome 9 probe (Metasystems, Germany) showing 1 normal chromosome 9 and the der(9) chromosome (green signal) (C).

Clinics and Pathology

Disease Myeloid malignancies mainly, acute lymphoblastic leukemia (ALL) and lymphomas.
Phenotype / cell stem origin Found in chronic and acute myeloid malignancies and mainly B-cell lymphoid malignancies.
Etiology Chronic myeloid malignancies in 12 (7M/5F aged 43 to 87 years, median 57 years): 1 chronic myeloproliferative disorder (MPD) (Hoo et al., 1987), 4 polycythemia vera (PV) (Chen et al., 1998; Najfeld et al., 2007) and 7 myelodysplastic syndrome (MDS) patients (Billstrom et al., 1988; Smadja et al., 1988; Iurlo et al., 1989; Wang et al., 1997; Lindvall et al., 2001; Stamatoullas et al., 2006; Najfeld et al., 2007). Among them, 3 patients developed MDS after chemotherapy for multiple myeloma (Smadja et al.,1988; Iurlo et al., 1989) or chronic lymphocytic leukemia (Wang et al., 1997).
Acute myeloid leukemia in 9 (4M/5F aged 13 to 79 years, median 67 years): 1 acute myeloblastic leukemia with maturation (AML-M2) (Poppe et al., 2004), 2 acute myelomonocytic leukemia (AML-M4) (Adriaansen et al., 1988; Poppe et al., 2004), 1 acute monoblastic leukemia without differentiation (AML-M5a) (Negrini et al., 1995), 1 acute megakaryoblastic leukemia (AML-M7) (Teyssier et al., 1987) and 4 acute myeloid leukemia, NOS (Pedersen et al., 1997; Van Limbergen et al., 2002; Shali et al., 2006; Moosavi et al., 2009). 1 of them developed acute myeloid leukemia 1 year after a myeloproliferative disorder was diagnosed (Negrini et al., 1995).
Acute lymphoblastic leukemia in 5 (4M/1F aged 10 and 14 years, 3 unknown); 3 patients were diagnosed with B-ALL (Heerema et al., 1992; Paulsson et al., 2015; Coyaud et al 2010) and 2 with T-ALL (Gladstone et al., 1998).
B-cell lymhoma in 13: diffuse large B-cell lymphoma (DLBCL) in 6 (3M/3F aged 18, 70, 73. 81 and 83 years, 2 unknown) (Mark et al., 1979; Mikraki et al., 1992; Ruminy et al., 2006; Chapiro et al., 2008; Bacher et al., 2011; Narayan et al., 2013), Hodgkin disease in 6 (3M/3F aged 12, 21, 25, 25 and 29 years, 1 unknown) (Tilly et al., 1991; Dohner et al., 1992; Schlegelberger et al., 1994; Cook et al., 2004) and a 62-years old male patient with extranodal marginal zone B-cell lymphoma (Van Roosbroeck et al., 2016).
T-cell lymhoma in 2: a 37- years old female diagnosed with angioimmunoblastic T-cell lymphoma (Lepretre et al., 2000) and a 78-years old female with adult T-cell lymphoma/leukemia ( (HTLV-1+) (Tanaka et al., 2001).
Epidemiology 41 patients; 22 males and 19 females aged 10 to 87 years; median 67 years.
Prognosis i(9)(p10) usually occurs within a complex karyotype, in itself with poor prognosis, therefore its appearance may be associated with advanced disease and unfavourable prognosis; the clinical significance of isolated i(9)(p10) in MPD is unclear.


As an isochromosome 9p can be misinterpreted as 9q deletion, a much more common finding in hematological malignancies, fluorescence in situ hybridization with locus specific probes of chromosome 9p/9q is a helpful method to confirm this less frequent abnormality.


Note Similar to i(5)(p10), described mainly in MDS and AML, two types of i(9)(p10) are observed: i(9)(p10) resulting in a loss of the long arm of the chromosome 9 (9q- and 9p trisomy) or it may be present as an extra +i(9)(p10), in addition to 2 normal chromosomes 9.
Cytogenetics Morphological Present as a supernumerary +i(9)(p10), in addition to two normal chromosomal 9 in 23 patients: 1 MPD (Hoo et al., 1987), 3 PV (Chen et al., 1998; Najfeld et al., 2007), 5 MDS (Billstrom et al., 1988; Smadja et al., 1988; Lindvall et al., 2001; Stamatoullas et al., 2006; Najfeld et al., 2007), 3 AML (Teyssier et al., 1987; Pedersen et al 1997; Van Limbergen et al., 2002), 1 ALL (Coyaud et al., 2010) and 10 B-cell lymphomas (Tilly et al., 1991; Dohner et al., 1992; Mikraki et al., 1992; Schlegelberger et al., 1994; Cook et al., 2004; Ruminy et al., 2006; Chapiro et al., 2008; Bacher et al., 2011; Narayan et al., 2013; Van Roosbroeck et al., 2016).
Additional anomalies Found as the sole extra i(9)(p10) in 1 MPD (Hoo et al., 1987) and 3 PV patients (Chen et al., 1998; Najfeld et al., 2007), in association with i(9)(q10) in 1 PV (Najfeld et al., 2007) and 1 ALL (Heerema et al., 1992). Associated with chromosome 5/chromosome 7 anomalies or their combination in 5 MDS (Iurlo et al., 1989; Wang et al., 1997; Lindvall et al., 2001; Stamatoullas et al., 2006; Najfeld et al., 2007) and 6 AML (Teyssier et al., 1987; Pedersen et al., 1997; Van Limbergen et al., 2002; Poppe et al., 2004; Shali et al., 2006; Moosavi et al., 2009) and found with t(9;11)(p21;q23) in 2 AML patients (Cuneo et al., 1993; Negrini et al., 1995). Found with del(6q), del(7q) in 1, del(5q),del(6q) in 1 (Gladstone et al., 1998) and t(6;14)(p22;q32),+del(7q) in 1 ALL (Coyaud et al 2010). Part of complex karyotypes associated with 14q32 rearrangements in DLBCL and part of hypedriploid/near triploid complex karyotypes in Hodgkin disease patients.

Result of the chromosomal anomaly

Fusion Protein
Oncogenesis Isochromosome i(9)(p10) represents a rare but recurrent chromosome abnormality in hematological malignancies, especially in chronic myeloid disorders, acute myeloid leukemia and B-cell lymphomas such as DLBCL and Hodgkin disease. The formation of i(9)(p10) induce a loss of the long arm of the chromosome 9 and duplication of its short arm, or less frequently it results only in an extra copy of 9p when 2 normal chromosomes 9 are present. In both cases, gain of chromosome material from 9p leading to extra copies of a gene or genes appears to be important in disease pathogenesis via gene dosage effect. Among them, the tyrosine kinase gene JAK2 on 9p24.1 might be a candidate gene as its numerical gain and structural rearrangements characterize both myeloid and B-lymphoid neoplasms. Gain and amplification of chromosomal sequences spanning JAK2 has been observed in both JAK2617V>F-positive and -negative patients with Philadelphia chromosome negative myeloproliferative disorders, with or without +9/+9p chromosomal abnormalities, indicating that amplification of a genes on 9p, and not deletion of genes from 9q, may play a role in the pathogenesis (Najfeld et al., 2007). JAK2 copy gain is also one of the most common genetic alterations in B-lymphoid neoplasms, especially Hodgkin lymphoma and primary mediastinal large B-cell lymphoma (Van Roosbroeck et al., 2016). Several of the imbalances described, including a recurrent 9p24.1 amplicon that includes JAK2 and immunoregulatory PD-1 ligand genes, leading to increased JAK2 protein expression activating the JAK2/STAT signaling pathway in a copy number-dependent manner.


Translocation (6;9) may be associated with a specific TdT-positive immunological phenotype in ANLL
Adriaansen HJ, van Dongen JJ, Hooijkaas H, Hählen K, van 't Veer MB, Löwenberg B, Hagemeijer A
Leukemia 1988 Mar;2(3):136-40
PMID 3347092
Several lymphoma-specific genetic events in parallel can be found in mature B-cell neoplasms
Bacher U, Haferlach T, Alpermann T, Kern W, Schnittger S, Haferlach C
Genes Chromosomes Cancer 2011 Jan;50(1):43-50
PMID 20960563
Bone marrow karyotype and prognosis in primary myelodysplastic syndromes
Billström R, Thiede T, Hansen S, Heim S, Kristoffersson U, Mandahl N, Mitelman F
Eur J Haematol 1988 Oct;41(4):341-6
PMID 3197821
The most frequent t(14;19)(q32;q13)-positive B-cell malignancy corresponds to an aggressive subgroup of atypical chronic lymphocytic leukemia
Chapiro E, Radford-Weiss I, Bastard C, Luquet I, Lefebvre C, Callet-Bauchu E, Leroux D, Talmant P, Mozziconacci MJ, Mugneret F, Struski S, Raynaud S, Andrieux J, Barin C, Jotterand M, Mossafa H, Ramond S, Terré C, Lippert E, Berger F, Felman P, Merle-Béral H, Bernard OA, Davi F, Berger R, Nguyen-Khac F
Leukemia 2008 Nov;22(11):2123-7
PMID 18449207
Gain of 9p in the pathogenesis of polycythemia vera
Chen Z, Notohamiprodjo M, Guan XY, Paietta E, Blackwell S, Stout K, Turner A, Richkind K, Trent JM, Lamb A, Sandberg AA
Genes Chromosomes Cancer 1998 Aug;22(4):321-4
PMID 9669670
Utility of routine classical cytogenetic studies in the evaluation of suspected lymphomas: results of 279 consecutive lymph node/extranodal tissue biopsies
Cook JR, Shekhter-Levin S, Swerdlow SH
Am J Clin Pathol 2004 Jun;121(6):826-35
PMID 15198354
Wide diversity of PAX5 alterations in B-ALL: a Groupe Francophone de Cytogenetique Hematologique study
Coyaud E, Struski S, Prade N, Familiades J, Eichner R, Quelen C, Bousquet M, Mugneret F, Talmant P, Pages MP, Lefebvre C, Penther D, Lippert E, Nadal N, Taviaux S, Poppe B, Luquet I, Baranger L, Eclache V, Radford I, Barin C, Mozziconacci MJ, Lafage-Pochitaloff M, Antoine-Poirel H, Charrin C, Perot C, Terre C, Brousset P, Dastugue N, Broccardo C
Blood 2010 Apr 15;115(15):3089-97
PMID 20160164
Clinical review on features and cytogenetic patterns in adult acute myeloid leukemia with lymphoid markers
Cuneo A, Ferrant A, Michaux JL, Boogaerts M, Demuynck H, Bosly A, Doyen C, Carli MG, Piva N, Castoldi G, et al
Leuk Lymphoma 1993 Mar;9(4-5):285-91
PMID 8348065
Recurring chromosome abnormalities in Hodgkin's disease
Döhner H, Bloomfield CD, Frizzera G, Frestedt J, Arthur DC
Genes Chromosomes Cancer 1992 Nov;5(4):392-8
PMID 1283328
Cytogenetic studies in patients from India with T-acute lymphoblastic leukemia
Gladstone B, Amare PS, Pai SK, Gopal R, Joshi S, Nair CN, Advani SH
Cancer Genet Cytogenet 1998 Oct 1;106(1):44-8
PMID 9772908
Cytogenetic analysis in relapsed childhood acute lymphoblastic leukemia
Heerema NA, Palmer CG, Weetman R, Bertolone S
Leukemia 1992 Mar;6(3):185-92
PMID 1564954
Double supernumerary isochromosome 9p in myeloproliferative syndrome
Hoo JJ, O'Brien S, Samuel I
Cancer Genet Cytogenet 1987 Dec;29(2):319-21
PMID 3479237
Cytogenetic and clinical investigations in 76 cases with therapy-related leukemia and myelodysplastic syndrome
Iurlo A, Mecucci C, Van Orshoven A, Michaux JL, Boogaerts M, Noens L, Bosly A, Louwagie A, Van Den Berghe H
Cancer Genet Cytogenet 1989 Dec;43(2):227-41
PMID 2598167
Chromosome abnormalities in peripheral T-cell lymphoma
Lepretre S, Buchonnet G, Stamatoullas A, Lenain P, Duval C, d'Anjou J, Callat MP, Tilly H, Bastard C
Cancer Genet Cytogenet 2000 Feb;117(1):71-9
PMID 10700871
Molecular cytogenetic characterization of acute myeloid leukemia and myelodysplastic syndromes with multiple chromosome rearrangements
Lindvall C, Nordenskjöld M, Porwit A, Björkholm M, Blennow E
Haematologica 2001 Nov;86(11):1158-64
PMID 11694401
Distinct patterns of chromosome abnormalities characterize childhood non-Hodgkin's lymphoma
Mikraki V, Jhanwar SC, Filippa DA, Wollner N, Chaganti RS
Br J Haematol 1992 Jan;80(1):15-20
PMID 1536806
Marker chromosomes are a significant mechanism of high-level RUNX1 gene amplification in hematologic malignancies
Moosavi SA, Sanchez J, Adeyinka A
Cancer Genet Cytogenet 2009 Feb;189(1):24-8
PMID 19167608
Numerical gain and structural rearrangements of JAK2, identified by FISH, characterize both JAK2617V>F-positive and -negative patients with Ph-negative MPD, myelodysplasia, and B-lymphoid neoplasms
Najfeld V, Cozza A, Berkofsy-Fessler W, Prchal J, Scalise A
Exp Hematol 2007 Nov;35(11):1668-76
PMID 17976519
PCDH10 promoter hypermethylation is frequent in most histologic subtypes of mature lymphoid malignancies and occurs early in lymphomagenesis
Narayan G, Xie D, Freddy AJ, Ishdorj G, Do C, Satwani P, Liyanage H, Clark L, Kisselev S, Nandula SV, Scotto L, Alobeid B, Savage D, Tycko B, O'Connor OA, Bhagat G, Murty VV
Genes Chromosomes Cancer 2013 Nov;52(11):1030-41
PMID 23929756
A novel t(9;11)(p22;q23) with ALL-1 gene rearrangement associated with progression of a myeloproliferative disorder to acute myeloid leukemia
Negrini M, Cuneo A, Nakamura T, Baffa R, Sabbioni S, Alder H, Castoldi G, Croce CM
Cancer Genet Cytogenet 1995 Aug;83(1):65-70
PMID 7656208
The genomic landscape of high hyperdiploid childhood acute lymphoblastic leukemia
Paulsson K, Lilljebjörn H, Biloglav A, Olsson L, Rissler M, Castor A, Barbany G, Fogelstrand L, Nordgren A, Sjögren H, Fioretos T, Johansson B
Nat Genet 2015 Jun;47(6):672-6
PMID 25961940
The monosomy 7 clone in interphase and metaphase cell population: a combined chromosome and primed in situ labeling study
Pedersen B, Koch J, Bendix Hansen K, Hindkjaer J, Lindbjerg Andersen C
Acta Haematol 1997;97(4):216-21
PMID 9158664
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
Two patterns of chromosomal breakpoint locations on the immunoglobulin heavy-chain locus in B-cell lymphomas with t(3;14)(q27;q32): relevance to histology
Ruminy P, Jardin F, Picquenot JM, Gaulard P, Parmentier F, Buchonnet G, Maisonneuve C, Tilly H, Bastard C
Oncogene 2006 Aug 10;25(35):4947-54
PMID 16619046
Cytogenetic findings and results of combined immunophenotyping and karyotyping in Hodgkin's disease
Schlegelberger B, Weber-Matthiesen K, Himmler A, Bartels H, Sonnen R, Kuse R, Feller AC, Grote W
Leukemia 1994 Jan;8(1):72-80
PMID 8289502
Cytogenetic studies of a series of 43 consecutive secondary myelodysplastic syndromes/acute myeloid leukemias: conventional cytogenetics, FISH, and multiplex FISH
Shali W, Hélias C, Fohrer C, Struski S, Gervais C, Falkenrodt A, Leymarie V, Lioure B, Raby P, Herbrecht R, Lessard M
Cancer Genet Cytogenet 2006 Jul 15;168(2):133-45
PMID 16843103
Double i(9p) in hematology
Smadja N, Krulik M, de Gramont A, Gonzalez-Canali G, Audebert AA
Cancer Genet Cytogenet 1988 Dec;36(2):217-9
PMID 3203313
Unusual complex hyperdiploid karyotypes in myelodysplastic syndromes
Stamatoullas A, Callat MP, Marreiros S, Tilly H, Bastard C
Cancer Genet Cytogenet 2006 Oct 15;170(2):129-32
PMID 17011983
Restricted chromosome breakpoint sites on 11q22-q23
Tanaka K, Eguchi M, Eguchi-Ishimae M, Hasegawa A, Ohgami A, Kikuchi M, Kyo T, Asaoku H, Dohy H, Kamada N
1 and 11q25 in various hematological malignancies without MLL/ALL-1 gene rearrangement Cancer Genet Cytogenet
PMID 11165319
Chromosomal subclonal evolution in paroxysmal nocturnal hemoglobinuria evolving into acute megakaryoblastic leukemia
Teyssier JR, Pigeon F, Behar C, Pignon B, Blaise AM
Cancer Genet Cytogenet 1987 Apr;25(2):259-64
PMID 3470116
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
Genomic alterations of the JAK2 and PDL loci occur in a broad spectrum of lymphoid malignancies
Van Roosbroeck K, Ferreiro JF, Tousseyn T, van der Krogt JA, Michaux L, Pienkowska-Grela B, Theate I, De Paepe P, Dierickx D, Doyen C, Put N, Cools J, Vandenberghe P, Wlodarska I
Genes Chromosomes Cancer 2016 May;55(5):428-41
PMID 26850007
dic(5;17): a recurring abnormality in malignant myeloid disorders associated with mutations of TP53
Wang P, Spielberger RT, Thangavelu M, Zhao N, Davis EM, Iannantuoni K, Larson RA, Le Beau MM
Genes Chromosomes Cancer 1997 Nov;20(3):282-91
PMID 9365836


This paper should be referenced as such :
Adriana Zamecnikova
Atlas Genet Cytogenet Oncol Haematol. 2019;23(8):224-227.
Free journal version : [ pdf ]   [ DOI ]
On line version :

External links

arrayMap (UZH-SIB Zurich)Morph ( 9950/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Morph ( 9874/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Morph ( 9867/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Morph ( 9891/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Morph ( 9910/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Morph ( 9920/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Morph ( 9705/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Morph ( 9827/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Morph ( 9680/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Morph ( 9650/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Morph ( 9699/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
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 : Fri Oct 8 16:35:33 CEST 2021

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

For comments and suggestions or contributions, please contact us