i(7)(q10) in myeloid malignancies

2017-08-01   Adriana Zamecnikova 

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


Isochromosome of the long arm of chromosome 7 is a known chromosomal abnormality in hematological malignancies that may be found in patients with Shwachman-Diamond syndrome, hepatosplenic T-cell lymphoma and acute lymphoblastic leukemia. In myeloid malignancies, i(7)(q10) may be found in acute myeloid leukemias and chronic myeloproliferative disorders, either as a solely anomaly or more frequently as a secondary anomaly associated with other additional anomalies.

Clinics and Pathology


Chronic myeloproliferative disorders, myelodysplastic syndromes, and acute myeloid leukemias (AML)


14 cases (10 males and 4 females, aged 5 to 67 years) were diagnosed with various chronic myeloproliferative disorders: 6 myelodysplastic syndrome (MDS) (Ref. in Table 1.), 6 chronic myeloid leukemia (CML), 1 essential thrombocythemia (ET) and 1 idiopathic myelofibrosis (IF) (Table 1).
There were 40 AML patients, with prevalence of acute megakaryoblastic leukemia (AML-M7) cases, diagnosed in 14 (Ref. in Table 2.), among them 8 diagnosed in patients with Downs syndrome (DS). The remaining AML cases were: 5 acute undifferentiated leukemia (AML-M0), 2 acute myeloblastic leukemia without maturation (FAB type M1), 4 acute myeloblastic leukemia with maturation (FAB type M2), 2 acute promyelocytic leukemia (FAB type M3), 2 acute myelomonocytic leukemia (FAB type M4), 3 acute monoblastic leukemia (FAB type M5), 2 acute erythroleukemia (FAB type M6) and 6 AML cases (Table 2).
35 male and 19 female patients aged 0 to 86 years (median 12 years); 25 patients were children aged 0 to 12 years ( median 1 years), among them 14 Downs syndrome patients aged 0 to 12 years (median 1 year); adult cases were 19 to 86 years old (median 55 years).
Table 1. i(7)(q10) in chronic myeloproliferative disorders and myelodysplastic syndromes
4M/5RAEB48,XY,add(5)(p15),i(7)(q10),del(13)(q12q14),der(14)t(14;17)(p11;q11),+21,+mar/88-93,XXYY,+der(1)t(1;19)(p13;q11),del(2)(p22),add(4)(p16),i(7)(q10)x2,+8,del(13)x2,der(14) ,der(17)t(11;17)(q13;p13)x2
6M/5MDS46,XY,i(7)(q10)/46,XY,del(20)(q11)      Shwachman-Diamond syndrome
12F/42MDS46,XX,i(7)(q10)/46,idem,del(11)(q14)      Fanconi anemia
13F/53IF48,XX,del(5)(q13q31),i(7)(q10),+8,add(11)(p15)      PDGFRB

1. Labal de Vinuesa et al., 1987; 2. Larripa et al., 1987; 3. Werner et al., 1991; 4. Tien et al., 1994; 5. Dror et al., 1998; 6. Dror et al., 1998; 7. Nakayama et al., 1999; 8. Marktel et al., 2003; 9. Tanaka et al., 2004; 10. Ohyashiki et al., 2008; 11. Fabarius et al., 2011; 12. Quentin et al., 2011; 13. Arefi et al., 2012; 14. Nadal et al., 2012
Abbreviations: M, male; F, female; RARS, refractory anemia with ringed sideroblasts; CML, chronic myeloid leukemia; RAEB, refractory anemia with excess of blasts; MDS, myelodysplastic syndrome; ET, essential thrombocythemia; IF, idiopathic myelofibrosis.
Table 2. i(7)(q10) in acute myeloid leukemias
 Sex/ AgeDiseaseKaryotype
4F/40AML-M246,XX,i(7)(q10) / 46,XX,del(1)(q?),i(7)(q10)
15F/0AML-M5 46,XX,i(7)(q10)
17F/86AML82-83,XX,-X,der(X)t(X;8)(q11;q11),del(1)(p11),der(1)t(1;9)(q32;q12),add(3)(q11),del(3)(p14),der(3)t(3;5)(q21;q13),der(4;17)(q10;q10),-5, del(5)(q15q22)x2,add(7)(q32),i(7)(q10),-8,-8,del(8)(q22),-9,del(10)(q24) x2,del(11)(p13)x2,add(12)(p11),-13,?dup(13)(q33q14),-14,-15,-15,-16,add(19)(p13),+2r,+2mar/82-83,idem,del(12)(q?)
26M/71AML-M651-54,X,del(X),+1,del(5),+del(5),+6,i(7)(q10),+8,t(11;19),t(12;15)(p13;q22),t(13;14)c,+14,+15, r(19),+20,+20,+21
32M/1AML-M047,XY,i(7)(q10),+21c / 47,XY,+1,der(1;8)(q10;q10),i(7)(q10),add(11)(q25),del(16)(q12),add(18)(p11),+21c/94,idemx2

1-2. Labal de Vinuesa et al., 1987; 3. Pui et al., 1987; 4. Iurlo et al., 1989; 5. Hayashi et al., 1990; 6. Bunin et al., 1991; 7. Levy et al., 1994; 8. Finke et al., 1994; 9. Martinez-Climent et al., 1995; 10. Roulston et al., 1995; 11. Secker-Walker et al., 1995; 12.Shikano et al., 1995; 13-14. Creutzig et al., 1996; 15.Cimino et al., 1997; 16. El-Rifai et al., 1997; 17. Andreasson et al., 1998; 18. Archimbaud et al., 1998; 19. Streubel et al., 1998; 20. Raimondi et al., 1999; 21. Grimwade et al., 2000; 22. Alvarez et al.,2001; 23. Shah et al., 2001; 24. Strehl et al., 2001; 25. Yamada et al., 2001; 26. Cigudosa et al 2003; 27. Roumier et al., 2003; 28. Tchinda et al., 2004; 29. Chang et al., 2005; 30. Bene et al., 2006; 31. Massey et al., 2006; 32. Wong et al., 2006; 33. Hama et al., 2008; 34. Hasle et al.,2008; 35. Radtke et al., 2009; 36. Duhoux et al., 2011; 37. Lundin et al., 2012; 38. Yoshida et al., 2013; 39. Xu et al., 2014; 40. Ono et al., 2015.
Abbreviations: M, male; F, female; AML-M2., acute myeloblastic leukemia with maturation; AML-M4, acute myelomonocytic leukemia; AML-M5; acute monoblastic leukemia; AML-M1, acute myeloblastic leukemia without maturation; AML-M7; acute megakaryoblastic leukemia; AML, acute myeloid leukemia; APL, acute promyelocytic leukemia; AML-M0; acute myeloblastic leukemia with minimal differentiation; AML-M6, acute erythroleukemia.


May depend on chronic versus acute disease and the presence of other karyotypic anomalies; likely unfavorable in association with disease progression and/or complex karyotypes.

Result of the Chromosomal Anomaly


Isochromosome of the long arm of chromosome 7 is a nonrandom chromosome anomaly in myeloid malignancies including acute myeloid leukemias, chronic myeloid leukemia, myelodysplastic syndromes and myeloproliferative neoplasms. Usually observed as an additional anomaly or is part of complex karyotypes, indicating involvement of genes from chromosome 7 in disease progression. i(7)(q10) results in a loss of the short arm (7p) and duplication of the long arm (7q) leading to a single copy of 7p and three copies of 7q resulting in genomic unbalances. The gain of genes on 7q as a result of isochromosome formation may play a significant role in the pathogenesis while loss of tumor suppressor gene or genes from 7p might be a required cooperating event.


Pubmed IDLast YearTitleAuthors
115794692001Frequent gain of chromosome 19 in megakaryoblastic leukemias detected by comparative genomic hybridization.Alvarez S et al
95291341998Fluorescence in situ hybridization analyses of hematologic malignancies reveal frequent cytogenetically unrecognized 12p rearrangements.Andreasson P et al
94369171998Clinical and biological characteristics of adult de novo and secondary acute myeloid leukemia with balanced 11q23 chromosomal anomaly or MLL gene rearrangement compared to cases with unbalanced 11q23 anomaly: confirmation of the existence of different entities with 11q23 breakpoint.Archimbaud E et al
225876852012Incidence and clinical characteristics of myeloproliferative neoplasms displaying a PDGFRB rearrangement.Arefi M et al
164371462006Near-tetraploid acute myeloid leukemias: an EGIL retrospective study of 25 cases.Béné MC et al
18296461991Chromosome 7 abnormalities in children with Down syndrome and preleukemia.Bunin N et al
159596002005Neoplastic disorders of hematopoiesis in children with Down's syndrome--a single institution experience in Taiwan.Chang HH et al
126191652003De novo erythroleukemia chromosome features include multiple rearrangements, with special involvement of chromosomes 11 and 19.Cigudosa JC et al
90290181997Multigenetic lesions in infant acute leukaemias: correlations with ALL-1 gene status.Cimino G 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
97665041998Malignant myeloid transformation with isochromosome 7q in Shwachman-Diamond syndrome.Dror Y et al
220394592011Refinement of 1p36 alterations not involving PRDM16 in myeloid and lymphoid malignancies.Duhoux FP et al
91290391997Prognostic value of metaphase-fluorescence in situ hybridization in follow-up of patients with acute myeloid leukemia in remission.El-Rifai W et al
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
81671791994Detection of chromosome 11q23 involving translocations by pulsed field gel electrophoresis.Finke J et al
109423712000Characterization of acute promyelocytic leukemia cases lacking the classic t(15;17): results of the European Working Party. Groupe Français de Cytogénétique Hématologique, Groupe de Français d'Hematologie Cellulaire, UK Cancer Cytogenetics Group and BIOMED 1 European Community-Concerted Action "Molecular Cytogenetic Diagnosis in Haematological Malignancies".Grimwade D et al
182754332008Acute megakaryoblastic leukaemia (AMKL) in children: a comparison of AMKL with and without Down syndrome.Hama A et al
180594802008Myeloid leukemia in children 4 years or older with Down syndrome often lacks GATA1 mutation and cytogenetics and risk of relapse are more akin to sporadic AML.Hasle H et al
2364166199014q32 translocations are associated with mixed-lineage expression in childhood acute leukemia.Hayashi Y et al
25981671989Cytogenetic and clinical investigations in 76 cases with therapy-related leukemia and myelodysplastic syndrome.Iurlo A et al
31214611987Chromosome studies in human hematologic diseases: II. Myelodysplastic syndromes.Larripa I et al
81180361994DNA rearrangements proximal to the EVI1 locus associated with the 3q21q26 syndrome.Levy ER et al
220724022012High frequency of BTG1 deletions in acute lymphoblastic leukemia in children with down syndrome.Lundin C et al
126512632003Chronic myeloid leukemia in chronic phase responding to imatinib: the occurrence of additional cytogenetic abnormalities predicts disease progression.Marktel S et al
76436161995Detection of 11q23/MLL rearrangements in infant leukemias with fluorescence in situ hybridization and molecular analysis.Martinez-Climent JA et al
164698742006A prospective study of the natural history of transient leukemia (TL) in neonates with Down syndrome (DS): Children's Oncology Group (COG) study POG-9481.Massey GV et al
227275092012LHX2 deregulation by juxtaposition with the IGH locus in a pediatric case of chronic myeloid leukemia in B-cell lymphoid blast crisis.Nadal N et al
104635861999Decreases in Ikaros activity correlate with blast crisis in patients with chronic myelogenous leukemia.Nakayama H et al
187864362008Recurrent der(9;18) in essential thrombocythemia with JAK2 V617F is highly linked to myelofibrosis development.Ohyashiki K et al
252660422015Acute megakaryoblastic leukemia with acquired trisomy 21 and GATA1 mutations in phenotypically normal children.Ono R et al
29521821987An analysis of leukemic cell chromosomal features in infants.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
196516012009Genomic analysis reveals few genetic alterations in pediatric acute myeloid leukemia.Radtke I 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
75794751995Therapy-related acute leukemia associated with t(11q23) after primary acute myeloid leukemia with t(8;21): a report of two cases.Roulston D et al
123933812003M0 AML, clinical and biologic features of the disease, including AML1 gene mutations: a report of 59 cases by the Groupe Français d'Hématologie Cellulaire (GFHC) and the Groupe Français de Cytogénétique Hématologique (GFCH).Roumier C et al
85471011995Abnormalities of 3q21 and 3q26 in myeloid malignancy: a United Kingdom Cancer Cytogenetic Group study.Secker-Walker LM et al
119114132001Widespread bone disease in acute myeloid leukaemia.Shah D et al
76562031995A t(11;14)(p13;q11) specific for T-cell malignancies in acute megakaryoblastic leukemia.Shikano T et al
111575012001Multiplex reverse transcriptase-polymerase chain reaction screening in childhood acute myeloblastic leukemia.Strehl S et al
95046351998Correlation of cytogenetic, molecular cytogenetic, and clinical findings in 59 patients with ANLL or MDS and abnormalities of the short arm of chromosome 12.Streubel B et al
153503032004Effect of interferon-alpha on chromosome abnormalities in treated chronic myelogenous leukemia patients.Tanaka H et al
145621222004A cryptic insertion (17;15) on both chromosomes 17 with lack of PML-RARA expression in a case of atypical acute promyelocytic leukemia.Tchinda J 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
19322981991Cytogenetics of chronic myelogenous leukemia (CML) correlated to the histopathology of bone marrow biopsies.Werner M et al
164343202006Isochromosome 7q in Down syndrome.Wong KF et al
243975942014Myeloid neoplasm with t(3;8)(q26;q24): report of six cases and review of the literature.Xu X et al
117946992001Distinctive multidrug sensitivity and outcome of acute erythroblastic and megakaryoblastic leukemia in children with Down syndrome.Yamada S et al
240567182013The landscape of somatic mutations in Down syndrome-related myeloid disorders.Yoshida K et al


Atlas Image
Figure 1. Partial karyotypes showing i(7)(q10) (A). Fluorescence in situ hybridization with Vysis LSI D7S486 (7q31) SpectrumOrange/ Vysis CEP 7 SpectrumGreen probe (Downers Grove, IL) hybridizing to bands 7q11 and 7q31, demonstrated 3 copies of the long arm of chromosome 7 (red signal) (B). Hybridization with Vysis whole chromosome 7 probe showing the normal and the i(7)(q10) chromosome (green) (C).


Adriana Zamecnikova

i(7)(q10) in myeloid malignancies

Atlas Genet Cytogenet Oncol Haematol. 2017-08-01

Online version: http://atlasgeneticsoncology.org/haematological/1244/i(7)(q10)-in-myeloid-malignancies