Monosomal karyotypes apart from complex karyotypes independently predict the outcome of myelodysplastic syndrome patients using a fluorescence in situ hybridization panel and conventional cytogenetics
Na Wang
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
School of Medicine, Shandong University, Jinan, China
Search for more papers by this authorHongzhi Xu
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
Search for more papers by this authorQing Li
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
Search for more papers by this authorJie Liu
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
Search for more papers by this authorXiaohui Sui
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
Search for more papers by this authorYujie Jiang
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
Search for more papers by this authorXiaosheng Fang
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
Search for more papers by this authorChangqing Zhen
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
Search for more papers by this authorMei Ding
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
Search for more papers by this authorDai Yuan
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
Search for more papers by this authorCorresponding Author
Lingyan Zhang
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
Correspondence
Xin Wang and Lingyan Zhang, Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Road, Jinan, Shandong 250021, China.
Emails: [email protected] (LZ), [email protected] (XW)
Search for more papers by this authorCorresponding Author
Xin Wang
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
School of Medicine, Shandong University, Jinan, China
Correspondence
Xin Wang and Lingyan Zhang, Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Road, Jinan, Shandong 250021, China.
Emails: [email protected] (LZ), [email protected] (XW)
Search for more papers by this authorNa Wang
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
School of Medicine, Shandong University, Jinan, China
Search for more papers by this authorHongzhi Xu
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
Search for more papers by this authorQing Li
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
Search for more papers by this authorJie Liu
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
Search for more papers by this authorXiaohui Sui
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
Search for more papers by this authorYujie Jiang
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
Search for more papers by this authorXiaosheng Fang
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
Search for more papers by this authorChangqing Zhen
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
Search for more papers by this authorMei Ding
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
Search for more papers by this authorDai Yuan
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
Search for more papers by this authorCorresponding Author
Lingyan Zhang
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
Correspondence
Xin Wang and Lingyan Zhang, Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Road, Jinan, Shandong 250021, China.
Emails: [email protected] (LZ), [email protected] (XW)
Search for more papers by this authorCorresponding Author
Xin Wang
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
School of Medicine, Shandong University, Jinan, China
Correspondence
Xin Wang and Lingyan Zhang, Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Road, Jinan, Shandong 250021, China.
Emails: [email protected] (LZ), [email protected] (XW)
Search for more papers by this authorAbstract
Introduction
The aim of the study was to analyze monosomal karyotype (MK) occurrence and the relationship between MKs and complex karyotypes (CKs) and to determine the prognostic significance of MKs in MDS patients based on conventional cytogenetic (CC) and fluorescence in situ hybridization (FISH) analyses.
Methods
CC and FISH analyses were conducted for 216 primary MDS patients. Follow-ups and statistical analysis were conducted.
Results
A total of 25 (11.6%) patients with MKs were identified by FISH and CC analyses, and 23 (92%) of these MKs were also CKs. Only 19 patients (8.8%) with MKs were identified by CC analysis. Patients with MKs had higher bone marrow (BM) blast counts (P = 0.006), incidence of very high risk according to International Prognostic Scoring System-Revised (IPSS-R) (P < 0.001), leukemic transformation (P = 0.003,) and death rates (P < 0.001) than those without MKs. Overall survival (OS) and progression-free survival (PFS) of MK or CK patients which were additionally detected by FISH and CC analyses had no statistical significance with those MK or CK patients detected by CC analyses separately. Multivariate analysis indicated that MK (P < 0.001), blast in BM (P < 0.001) and age (P = 0.028) were inferior independent prognostic factors in OS, whereas CK (P = 0.003) was the inferior independent prognostic factor in PFS.
Conclusion
The MDS FISH panel may provide additional information for defining MKs beyond CC analysis. MK was an important indicator of OS in MDS patients, and CK indicated inferior disease progression but did not influence OS according to CC and FISH analyses.
CONFLICTS OF INTEREST
The authors have no conflicts of interest to declare.
REFERENCES
- 1Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016; 127: 2391-2405.
- 2Vardiman JW, Thiele J, Arber DA, 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: 937-951.
- 3Greenberg PL, Tuechler H, Schanz J, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012; 120: 2454-2465.
- 4Pozdnyakova O, Miron PM, Tang G, et al. Cytogenetic abnormalities in a series of 1,029 patients with primary myelodysplastic syndromes: a report from the US with a focus on some undefined single chromosomal abnormalities. Cancer. 2008; 113: 3331-3340.
- 5Haase D, Germing U, Schanz J, et al. New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients. Blood. 2007; 110: 4385-4395.
- 6Greenberg P, Cox C, LeBeau MM, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997; 89: 2079-2088.
- 7Malcovati L, Germing U, Kuendgen A, et al. Time-dependent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes. J Clin Oncol. 2007; 25: 3503-3510.
- 8Morel P, Hebbar M, Lai JL, et al. Cytogenetic analysis has strong independent prognostic value in de novo myelodysplastic syndromes and can be incorporated in a new scoring system: a report on 408 cases. Leukemia. 1993; 7: 1315-1323.
- 9Patnaik MM, Hanson CA, Hodnefield JM, et al. Monosomal karyotype in myelodysplastic syndromes, with or without monosomy 7 or 5, is prognostically worse than an otherwise complex karyotype. Leukemia. 2011; 25: 266-270.
- 10Belli CB, Bengio R, Aranguren PN, et al. Partial and total monosomal karyotypes in myelodysplastic syndromes: comparative prognostic relevance among 421 patients. Am J Hematol. 2011; 86: 540-545.
- 11Gangat N, Patnaik MM, Begna K, et al. Evaluation of revised IPSS cytogenetic risk stratification and prognostic impact of monosomal karyotype in 783 patients with primary myelodysplastic syndromes. Am J Hematol. 2013; 88: 690-693.
- 12McQuilten ZK, Sundararajan V, Andrianopoulos N, et al. Monosomal karyotype predicts inferior survival independently of a complex karyotype in patients with myelodysplastic syndromes. Cancer. 2015; 121: 2892-2899.
- 13Breems DA, Van Putten WL, De Greef GE, et al. Monosomal karyotype in acute myeloid leukemia: a better indicator of poor prognosis than a complex karyotype. J Clin Oncol. 2008; 26: 4791-4797.
- 14Valcarcel D, Adema V, Sole F, et al. Complex, not monosomal, karyotype is the cytogenetic marker of poorest prognosis in patients with primary myelodysplastic syndrome. J Clin Oncol. 2013; 31: 916-922.
- 15Itzykson R, Thepot S, Eclache V, et al. Prognostic significance of monosomal karyotype in higher risk myelodysplastic syndrome treated with azacitidine. Leukemia. 2011; 25: 1207-1209.
- 16Schanz J, Tuchler H, Sole F, et al. Monosomal karyotype in MDS: explaining the poor prognosis? Leukemia. 2013; 27: 1988-1995.
- 17Simons A, Shaffer LG, Hastings RJ. Cytogenetic nomenclature: changes in the ISCN 2013 compared to the 2009 edition. Cytogenet Genome Res. 2013; 141: 520-6.
- 18Pasquini MC, Zhang MJ, Medeiros BC, et al. Hematopoietic cell transplantation outcomes in monosomal karyotype myeloid malignancies. Biol Blood Marrow Transplant. 2016; 22: 248-257.
- 19Ustun C, Trottier BJ, Sachs Z, et al. Monosomal karyotype at the time of diagnosis or transplantation predicts outcomes of allogeneic hematopoietic cell transplantation in myelodysplastic syndrome. Biol Blood Marrow Transplant. 2015; 21: 866-872.
- 20Wudhikarn K, Van Rheeden R, Leopold C, et al. Outcome of allogeneic stem cell transplantation in myelodysplastic syndrome patients: prognostic implication of monosomal karyotype. Eur J Haematol. 2012; 89: 294-301.
- 21van Gelder M, de Wreede LC, Schetelig J, et al. Monosomal karyotype predicts poor survival after allogeneic stem cell transplantation in chromosome 7 abnormal myelodysplastic syndrome and secondary acute myeloid leukemia. Leukemia. 2013; 27: 879-888.
- 22Koenecke C, Gohring G, de Wreede LC, et al. Impact of the revised International Prognostic Scoring System, cytogenetics and monosomal karyotype on outcome after allogeneic stem cell transplantation for myelodysplastic syndromes and secondary acute myeloid leukemia evolving from myelodysplastic syndromes: a retrospective multicenter study of the European Society of Blood and Marrow Transplantation. Haematologica. 2015; 100: 400-408.
- 23Xing R, Li C, Gale RP, et al. Monosomal karyotype is an independent predictor of survival in patients with higher-risk myelodysplastic syndrome. Am J Hematol. 2014; 89: E163-E168.
- 24Yang YT, Hou HA, Liu CY, et al. IPSS-R in 555 Taiwanese patients with primary MDS: Integration of monosomal karyotype can better risk-stratify the patients. Am J Hematol. 2014; 89: E142-E149.
- 25Zhang T, Xu Y, Pan J, et al. Monosomal karyotype of chromosome 5/7 was an independent poor prognostic factor for Chinese myelodysplastic syndrome patients. Cancer Genet. 2016; 209: 423-429.
- 26Hwang KL, Song MK, Shin HJ, et al. Monosomal and complex karyotypes as prognostic parameters in patients with International Prognostic Scoring System higher risk myelodysplastic syndrome treated with azacitidine. Blood Res. 2014; 49: 234-240.
- 27Alam N, Atenafu EG, Kuruvilla J, et al. Outcomes of patients with therapy-related AML/myelodysplastic syndrome (t-AML/MDS) following hematopoietic cell transplantation. Bone Marrow Transplant. 2015; 50: 1180-1186.
- 28Kayser S, Zucknick M, Dohner K, et al. Monosomal karyotype in adult acute myeloid leukemia: prognostic impact and outcome after different treatment strategies. Blood. 2012; 119: 551-558.
- 29Strickland SA, Sun Z, Ketterling RP, et al. Independent prognostic significance of monosomy 17 and impact of karyotype complexity in monosomal karyotype/complex karyotype acute myeloid leukemia: results from four ECOG-ACRIN prospective therapeutic trials. Leuk Res. 2017; 59: 55-64.
- 30Rigolin GM, Bigoni R, Milani R, et al. Clinical importance of interphase cytogenetics detecting occult chromosome lesions in myelodysplastic syndromes with normal karyotype. Leukemia. 2001; 15: 1841-1847.
- 31Bernasconi P, Cavigliano PM, Boni M, et al. Is FISH a relevant prognostic tool in myelodysplastic syndromes with a normal chromosome pattern on conventional cytogenetics? A study on 57 patients. Leukemia. 2003; 17: 2107-2112.
- 32Merkel D, Soffer S, Novikov I, et al. Is fluorescence in-situ hybridization sufficient in patients with myelodysplastic syndromes and insufficient cytogenetic testing? Leuk Lymphoma. 2019; 60: 764-771.
- 33Raza S, TaherNazerHussain F, Patnaik M, et al. Autosomal monosomies among 24,262 consecutive cytogenetic studies: prevalence, chromosomal distribution and clinicopathologic correlates of sole abnormalities. Am J Hematol. 2011; 86: 353-356.
- 34Tibiletti MG. Interphase FISH as a new tool in tumor pathology. Cytogenet Genome Res. 2007; 118: 229-236.
Citing Literature
