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i(7)(q10) in myeloid malignancies

Written2017-08Adriana Zamecnikova
Kuwait Cancer Control Center, Department of Hematology, Laboratory of Cancer Genetics, Kuwait;

Abstract 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.

Keywords Isochromosome 7; myeloid malignancies.

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ICD-Topo C420,C421,C424
ICD-Morpho 9975/3 Chronic myelogenous leukaemia, BCR-ABL1 positive; Myeloproliferative neoplasm, unclassifiable; Myelodysplastic/myeloproliferative neoplasm, unclassifiable
ICD-Morpho 9961/3 Primary myelofibrosis
ICD-Morpho 9962/3 Essential thrombocythaemia
ICD-Morpho 9920/3 Therapy-related myeloid neoplasms
ICD-Morpho 9982/3 Refractory anemia with ring sideroblasts associated with marked thrombocytosis; Refractory anaemia with ring sideroblasts
ICD-Morpho 9983/3 Refractory anaemia with excess blasts
ICD-Morpho 9989/3 Myelodysplastic syndrome, unclassifiable
ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
ICD-Morpho 9866/3 Acute promyelocytic leukaemia with t(15;17)(q22;q12); PML-RARA
ICD-Morpho 9872/3 AML with minimal differentiation; Myeloid sarcoma
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 9840/3 Acute erythroid leukaemia
ICD-Morpho 9910/3 Acute megakaryoblastic leukaemia
Atlas_Id 1244
  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).

Clinics and Pathology

Disease Chronic myeloproliferative disorders, myelodysplastic syndromes, and acute myeloid leukemias (AML)
Epidemiology 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 Down's 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 Down's 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.
Prognosis 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.


Additional anomalies Sole anomaly in 2 MDS (Labal de Vinuesa et al., 1987; Dror et al., 1998) and 10 AML patients (Labal de Vinuesa et al., 1987; Pui et al., 1987; Iurlo et al., 1989; Creutzig et al., 1996; Cimino et al., 1997; Roumier et al., 2003; Chang et al., 2005; Massey et al., 2006; Lundin et al., 2012), 5 of them were DS patients with +21 (Pui et al., 1987; Creutzig et al., 1996; Chang et al., 2005; Massey et al., 2006; Lundin et al., 2012). Found as a sole addition anomaly to t(9;22) in 5 out of 6 CML patients (Werner et al., 1991; Nakayama et al., 1999; Marktel et al., 2003; Tanaka et al., 2004; Fabarius et al., 2011) and in association with t(9;14)(q33;q32) in 1 (Nadal et al., 2012). Associated with i(17)(q10) in 1 MDS (Larripa et al., 1987), del(20)(q11) in patient with MDS and Shwachman-Diamond syndrome (Dror et al., 1998), del(11)(q14) in MDS in a Fanconi anemia patient (Quentin et al., 2011), del(5)(q13q31), PDGFRB rearrangement and +8 in idiopathic myelofibrosis (Arefi et al., 2012) and found in a sideline with +8, +21 in the ET case (Ohyashiki et al., 2008). Highly complex anomalies in 1 MDS (Tien et al., 1994). Among the AML cases, associated with inv(3) in 2 (Levy et al., 1994; Secker-Walker et al., 1995), t(11;19)(q23;p13) in 1 (Finke et al., 1994), t(11;18)(q23;p11) in 1 (Roulston et al., 1995) and t(11;17)(q23;q21) in the AML-M3 patient (Grimwade et al., 2000). Various limited anomalies in 8 (Creutzig et al., 1996; El-Rifai et al., 1997; Streubel et al., 1998; Raimondi et al., 1999; Shah et al., 2001; Yamada et al., 2001; Duhoux et al., 2011; Ono et al., 2015) and higly complex karyotypes in the remaing AML patients.

Result of the chromosomal anomaly

Fusion Protein
Oncogenesis 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.


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This paper should be referenced as such :
Adriana Zamecnikova
i(7)(q10) in myeloid malignancies
Atlas Genet Cytogenet Oncol Haematol. 2018;22(10):435-441.
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