Advertisement

Prevalence of Chromosome 7 Abnormalities in Myelodysplastic Syndrome and Acute Myeloid Leukemia: A Single Center Study and Brief Literature Review

  • Ruchi Gupta
  • Shivangi Harankhedkar
  • Khaliqur Rahman
  • Manish K. Singh
  • Dinesh Chandra
  • Navkirti Mittal
  • Anshul Gupta
  • Soniya Nityanand
Original Article
  • 71 Downloads

Abstract

Chromosome 7 abnormalities in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) heralds a poor prognosis. However its prevalence, morphological characteristics and clinical impact in MDS and AML in Indian subcontinent is sparsely reported. This was an observational cross-sectional study performed to evaluate the clinico-pathological profiles of MDS/AML patients with chromosome 7 abnormalities over a period of 4 years. 724 cases of MDS (n = 150) and AML (n = 574) were evaluated. Abnormal karyotype was detected in 49% (43/88) patients of MDS and 44% (127/289) cases of AML. Chromosome 7 abnormalities were detected in 18% cases of MDS (16/88) and 6.5% (19/289) cases of AML. Sole chromosome 7 abnormalities were detected in 5.7% (5/88) and 2.7% (8/289) and in adjunct to complex abnormalities in 7.9 and 3.1% cases of MDS and AML respectively. Morphologically, dyserythropoiesis, dysmyelopoiesis and eosinophilia were seen in 100, 66 and 56% cases of MDS and 38, 40 and 21% cases of AML. Majority of the patients had an aggressive natural course and outcome was dismal. Chromosome 7 abnormalities are strongly associated with the presence of morphological dysplasia and eosinophilia, irrespective of the type of aberration. It is invariably associated with very poor outcome.

Keywords

MDS AML Chromosome 7 Morphology Cytogenetics 

Notes

Compliance with Ethical Standards

Conflict of interest

None.

Ethical Standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

References

  1. 1.
    Scherer SW, Cheung J, MacDonald JR et al (2003) Human chromosome 7: DNA sequence and biology. Science 300:767–772CrossRefGoogle Scholar
  2. 2.
    Hillier LW, Fulton RS, Fulton LA et al (2003) The DNA sequence of human chromosome 7. Nature 424:157–164CrossRefGoogle Scholar
  3. 3.
    Heim S (1992) Cytogenetic findings in primary and secondary MDS. Leuk Res 16:43–46CrossRefGoogle Scholar
  4. 4.
    Kardos G, Baumann I, Passmore SJ et al (2003) Refractory anemia in childhood: a retrospective analysis of 67 patients with particular reference to monosomy 7. Blood 102:1997–2003CrossRefGoogle Scholar
  5. 5.
    Grimwade D, Hills RK, Moorman AV et al (2010) Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood 116:354–365CrossRefGoogle Scholar
  6. 6.
    Chen Z, Pasquini M, Hong B, DeHart S, Heikens M, Tsai S (2005) The human Penumbra gene is mapped to a region on chromosome 7 frequently deleted in myeloid malignancies. Cancer Genet Cytogenet 162:95–98CrossRefGoogle Scholar
  7. 7.
    Johnson E, Cotter FE (1997) Monosomy 7 and 7q− associated with myeloid malignancy. Blood Rev 11:46–55CrossRefGoogle Scholar
  8. 8.
    Honda H, Nagamachi A, Inaba T (2015) 7/7q− syndrome in myeloid-lineage hematopoietic malignancies: attempts to understand this complex disease entity. Oncogene 34:2413–2425CrossRefGoogle Scholar
  9. 9.
    McNerney ME, Brown CD, Wang X, Bartom ET, Karmakar S, Bandlamudi C et al (2013) CUX1 is a haploinsufficient tumor suppressor gene on chromosome 7 is frequently inactivated in acute myeloid leukemia. Blood 121:975–983CrossRefGoogle Scholar
  10. 10.
    Basiricò R, Pirrotta R, Fabbiano F et al (2003) Submicroscopic deletions in the 7q region are associated with recurrent chromosome abnormalities in acute leukemia. Haematologica 88:429–437PubMedGoogle Scholar
  11. 11.
    Cigognini D, Corneo G, Fermo E, Zanella A, Tripputi P (2007) HIC gene, a candidate suppressor gene within a minimal region of loss at 7q31.1 in myeloid neoplasms. Leuk Res 31:477–482CrossRefGoogle Scholar
  12. 12.
    Brezinová J, Zemanová Z, Ransdorfová S et al (2007) Structural aberrations of chromosome 7 revealed by a combination of molecular cytogenetic techniques in myeloid malignancies. Cancer Genet Cytogenet 173:10–16CrossRefGoogle Scholar
  13. 13.
    Graux C, Cools J, Michaux L, Vandenberghe P, Hagemeijer A (2006) Cytogenetics and molecular genetics of T-cell acute lymphoblastic leukemia: from thymocyte to lymphoblast. Leukemia 20:1496–1510CrossRefGoogle Scholar
  14. 14.
    Döhner K, Brown J, Hehmann U et al (1998) Molecular cytogenetic characterization of a critical region in bands 7q35–q36 commonly deleted in malignant myeloid disorders. Blood 92:4031–4035PubMedGoogle Scholar
  15. 15.
    Kumar S, White DL, Takai S et al (1995) Apoptosis regulatory gene NEDD2 maps to human chromosome segment 7q34–35, a region frequently affected in haematological neoplasm. Hum Genet 95:641CrossRefGoogle Scholar
  16. 16.
    Solé F, Espinet B, Sanz GF et al (2000) Incidence, characterization and prognostic significance of chromosomal abnormalities in 640 patients with primary myelodysplastic syndromes. GrupoCooperativoEspañol de CitogenéticaHematológica. Br J Haematol 108:346–356CrossRefGoogle Scholar
  17. 17.
    Kardos G, Baumann I, Passmore SJ et al (2003) Refractory anemia in childhood: a retrospective analysis of 67 patients with particular reference to monosomy. Blood 102:1997–2003CrossRefGoogle Scholar
  18. 18.
    Grimwade D, Hills RK, Moorman AV et al (2010) Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood 116:354–365CrossRefGoogle Scholar
  19. 19.
    Neukirchen J, Lauseker M, Blum S et al (2014) Validation of the revised international prognostic scoring system (IPSS-R) in patients with myelodysplastic syndrome: a multicenter study. Leuk Res 38:57–64CrossRefGoogle Scholar
  20. 20.
    O’Donnell MR, Tallman MS, Abboud CN et al (2017) Acute myeloid leukemia, version 3.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Cancer Netw 15:926–957CrossRefGoogle Scholar
  21. 21.
    Vundinti BR, Kerketta L, Jijina F, Ghosh K (2009) Cytogenetic study of myelodysplastic syndrome from India. Indian J Med Res 130:155–159PubMedGoogle Scholar
  22. 22.
    Varma N, Varma S (2008) Proliferative indices, cytogenetics, immunophenotype and other prognostic parameters in myelodysplastic syndromes. Indian J Pathol Microbiol 51:97–101CrossRefGoogle Scholar
  23. 23.
    Gupta R, Rahman K, Singh MK, Kumari S, Yadav G, Nityanand S (2017) Clinico-pathological spectrum and novel karyotypic findings in myelodysplastic syndrome: experience of a tertiary care center in India. Mediterr J Hematol Infect Dis 9:e2017048CrossRefGoogle Scholar
  24. 24.
    Amare PSK, Jain H, Setal K (2016) Cytogenetic profile in 7209 Indian patients with de novo acute leukemia: a single centre study from India. J Cancer Ther 7:530–544CrossRefGoogle Scholar
  25. 25.
    Philip C, George B, Ganapule A et al (2015) Acute myeloid leukaemia: challenges and real world data from India. Br J Haematol 170:110–117CrossRefGoogle Scholar
  26. 26.
    Kayser S, Zucknick M, Döhner K et al (2012) Monosomal karyotype in adult acute myeloid leukemia: prognostic impact and outcome after different treatment strategies. Blood 119:551–558CrossRefGoogle Scholar
  27. 27.
    Haase D, Germing U, Schanz J et al (2007) New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients. Blood 110:4385–4395CrossRefGoogle Scholar
  28. 28.
    Hasle H, Alonzo TA, Auvrignon A, Behar C, Chang M, Creutzig U et al (2007) Monosomy 7 and deletion 7q in children and adolescents with acute myeloid leukemia: an international retrospective study. Blood 109:4641–4647CrossRefGoogle Scholar
  29. 29.
    Schanz J, Tuchler H, Sole F et al (2012) New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge. J Clin Oncol 30:820–829CrossRefGoogle Scholar
  30. 30.
    Gangat N, Patnaik NM, Begna K, Kourelis T, Kali A, Elliot MA (2015) Primary myelodysplastic syndrome: The Mayo clinic experience with 1000 patients. Mayo Clin Proc 90:1623–1638CrossRefGoogle Scholar
  31. 31.
    Byrd JC, Mrózek K, Dodge RK, Carroll AJ, Edwards CG, Arthur DC et al (2002) Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood 100:4325–4336CrossRefGoogle Scholar
  32. 32.
    Cheng Y, Wang Y, Wang H, Chen Z, Lou J, Xu H et al (2009) Cytogenetic profile of de novo acute myeloid leukemia: a study based on 1432 patients in a single institution of China. Leukemia 23:1801–1806CrossRefGoogle Scholar
  33. 33.
    Grimwade D, Walker H, Oliver F, Wheatley K, Harrison C, Harrison G et al (1998) The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 Trial. Blood 92:2322–2333Google Scholar
  34. 34.
    Qu S, Xu Z, Zhang Y, Qin T, Zhang T, Cui R et al (2012) Impacts of cytogenetic categories in the Revised International Prognostic Scoring System on the prognosis of primary myelodysplastic syndromes: results of a single-center study. Leuk Lymphoma 53:940–946CrossRefGoogle Scholar
  35. 35.
    Hussain FT, Nguyen EP, Raza S, Knudson R, Pardanani A, Hanson CA et al (2012) Sole abnormalitiesof chromosome 7 in myeloid malignancies: spectrum, histopathologic correlates, and prognostic implications. Am J Hematol 87:684–686CrossRefGoogle Scholar
  36. 36.
    Matsushima T, Handa H, Yokohama A, Nagasaki J, Koiso H, Kin Y et al (2003) Prevalence and clinical characteristics of myelodysplastic syndrome with bone marrow eosinophilia or basophilia. Blood 101:3386–3390CrossRefGoogle Scholar
  37. 37.
    Matsushima T, Murakami H, Sawamura M et al (1993) Myelodysplastic syndrome with eosinophilia in bone marrow. Br J Haematol 84:636–638CrossRefGoogle Scholar

Copyright information

© Indian Society of Hematology and Blood Transfusion 2018

Authors and Affiliations

  • Ruchi Gupta
    • 1
  • Shivangi Harankhedkar
    • 1
  • Khaliqur Rahman
    • 1
  • Manish K. Singh
    • 1
  • Dinesh Chandra
    • 1
  • Navkirti Mittal
    • 1
  • Anshul Gupta
    • 1
  • Soniya Nityanand
    • 1
  1. 1.Department of Hematology, I BlockSanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS)LucknowIndia

Personalised recommendations