Myeloid neoplasms with isolated isochromosome 17q: a yet to be defined entity

Main Article Content

Eleftheria Lamprianidou
Chryssoula Kordella
Menelaos Papoutselis
Zoi Bezyrgiannidou
Evangelia Nakou
Spyros Papamichos
Emmanouil Spanoudakis
Andreas Giannopoulos
Katerina Zoi
Ioannis Kotsianidis


isochromosome, MDS, spliceosome


It has been suggested that myeloid neoplasms with isolated isochromosome 17q[MN i(17q)] comprise a distinct entity with poor prognosis. However, literature reports show a considerable clinical and molecular heterogeneity. We describe a 58-year-old male patient who was diagnosed as refractory anemia with multilineage dysplasia and ringed sideroblasts with isolated i(17q). Though he initially responded well to erythropoietin, he gradually progressed to an aggressive form of MDS/MPN refractory to azacytidine and died 29 months after first diagnosis. Notably, in contrast to disease advancement, his karyotype reverted to normal, whereas his mutational profile remained unchanged. To our knowledge this is the first report of karyotype normalization during disease progression in patients with MN i(17q), suggesting that the i(17q) anomaly is dispensable for the leukemic transformation and highlighting the underlying clinical and molecular complexity which both have to be resolved before the establishment of MN with isolated i(17q) as a distinct entity.


Download data is not yet available.

Abstract 1604
PDF Downloads 511
HTML Downloads 671


1. Mertens F, Johansson B, Mitelman F. Isochromosomes in neoplasia. Genes Chromosomes Cancer. 1994;10(4):221-30.

2. Fioretos T, Strombeck B, Sandberg T, Johansson B, Billstrom R, Borg A, et al. Isochromosome 17q in blast crisis of chronic myeloid leukemia and in other hematologic malignancies is the result of clustered breakpoints in 17p11 and is not associated with coding TP53 mutations. Blood. 1999;94(1):225-32.

3. Kanagal-Shamanna R, Luthra R, Yin CC, Patel KP, Takahashi K, Lu X, et al. Myeloid neoplasms with isolated isochromosome 17q demonstrate a high frequency of mutations in SETBP1, SRSF2, ASXL1 and NRAS. Oncotarget. 2016;7(12):14251-8.

4. Mitelman F, Brandt L, Nilsson PG. Relation among occupational exposure to potential mutagenic/carcinogenic agents, clinical findings, and bone marrow chromosomes in acute nonlymphocytic leukemia. Blood. 1978;52(6):1229-37.

5. Kanagal-Shamanna R, Bueso-Ramos CE, Barkoh B, Lu G, Wang S, Garcia-Manero G, et al. Myeloid neoplasms with isolated isochromosome 17q represent a clinicopathologic entity associated with myelodysplastic/myeloproliferative features, a high risk of leukemic transformation, and wild-type TP53. Cancer. 2012;118(11):2879-88.

6. Visconte V, Tabarroki A, Zhang L, Hasrouni E, Gerace C, Frum R, et al. Clinicopathologic and molecular characterization of myeloid neoplasms harboring isochromosome 17(q10). American journal of hematology. 2014;89(8):862.

7. McClure RF, Dewald GW, Hoyer JD, Hanson CA. Isolated isochromosome 17q: a distinct type of mixed myeloproliferative disorder/myelodysplastic syndrome with an aggressive clinical course. British journal of haematology. 1999;106(2):445-54.

8. Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114(5):937-51.

9. Lazarevic V, Djordjevic V, Magic Z, Marisavljevic D, Colovic M. Refractory anemia with ring sideroblasts associated with i(17q) and mutation of the TP53 gene. Cancer Genet Cytogenet. 2002;136(1):86-9.

10. Becher R, Carbonell F, Bartram CR. Isochromosome 17q in Ph1-negative leukemia: a clinical, cytogenetic, and molecular study. Blood. 1990;75(8):1679-83.

11. Adema V, Larrayoz MJ, Calasanz MJ, Palomo L, Patino-Garcia A, Agirre X, et al. Correlation of myelodysplastic syndromes with i(17)(q10) and TP53 and SETBP1 mutations. British journal of haematology. 2015;171(1):137-41.

12. Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Sole F, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120(12):2454-65.

13. Lai JL, Preudhomme C, Zandecki M, Flactif M, Vanrumbeke M, Lepelley P, et al. Myelodysplastic syndromes and acute myeloid leukemia with 17p deletion. An entity characterized by specific dysgranulopoiesis and a high incidence of P53 mutations. Leukemia. 1995;9(3):370-81.

14. Damm F, Itzykson R, Kosmider O, Droin N, Renneville A, Chesnais V, et al. SETBP1 mutations in 658 patients with myelodysplastic syndromes, chronic myelomonocytic leukemia and secondary acute myeloid leukemias. Leukemia. 2013;27(6):1401-3.

15. Meggendorfer M, Haferlach C, Zenger M, Macijewski K, Kern W, Haferlach T. The landscape of myeloid neoplasms with isochromosome 17q discloses a specific mutation profile and is characterized by an accumulation of prognostically adverse molecular markers. Leukemia. 2016;30(7):1624-7.

16. Makishima H, Visconte V, Sakaguchi H, Jankowska AM, Abu Kar S, Jerez A, et al. Mutations in the spliceosome machinery, a novel and ubiquitous pathway in leukemogenesis. Blood. 2012;119(14):3203-10.

17. Przychodzen B, Jerez A, Guinta K, Sekeres MA, Padgett R, Maciejewski JP, et al. Patterns of missplicing due to somatic U2AF1 mutations in myeloid neoplasms. Blood. 2013;122(6):999-1006.

18. Schnittger S, Kohl TM, Haferlach T, Kern W, Hiddemann W, Spiekermann K, et al. KIT-D816 mutations in AML1-ETO-positive AML are associated with impaired event-free and overall survival. Blood. 2006;107(5):1791-9.

19. Schlenk RF, Dohner K, Krauter J, Frohling S, Corbacioglu A, Bullinger L, et al. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. The New England journal of medicine. 2008;358(18):1909-18.

20. Bacher U, Haferlach T, Kern W, Haferlach C, Schnittger S. A comparative study of molecular mutations in 381 patients with myelodysplastic syndrome and in 4130 patients with acute myeloid leukemia. Haematologica. 2007;92(6):744-52.