Cytogenetic Abnormalities Lead to Poor Prognosis in Patients with Myelofibrosis, Especially Postessential Thrombocythemia Myelofibrosis and Postpolycythemia Vera Myelofibrosis: A Multicenter Retrospective Study
Authors: Feng Qiutian , Huang Jian 
Published: December 2024

For patients with myelofibrosis (MF), personalized treatment planning based on disease risk stratification and symptom assessment is typically carried out. Some prognostic scoring systems applicable to overt Primary myelofibrosis(overt PMF) patients may not accurately categorize the prognosis of postessential thrombocythemia myelofibrosis (post-ET MF) and postpolycythemia vera myelofibrosis (post-PV MF) patients. Currently, the prognostic model for myelofibrosis secondary to postpolycythemia vera(PV) and thrombocythemia(ET) (MYSEC-PM) involves only clinical features and driver gene mutations, without stratified assessment of their cellular genetic characteristics. Here, we conducted a retrospective study of 338 MF patients in 6 hematooncology centers between 01 October 2013 and 30 November 2023. By analyzing the correlation and differences between the cellular genetic characteristics of patients with different types of MF and clinical factors, gene mutations, and survival prognosis, we aimed to provide guidance for clinical diagnosis, treatment, and prognosis assessment of different types of MF, especially post-ET MF and post-PV MF.

Chromosomal results for 338 MF patients revealed 253 patients with a normal karyotype (74.9%) and 85 patients with an abnormal karyotype (25.1%). When comparing the distribution of abnormal karyotypes among the different types of MF, the most common abnormal karyotypes in overt PMF patients were +8 (4.2%) and -20/20q- (4.2%), followed by -13/13q- (3.8%). The most common abnormal karyotype in post-ET MF patients was trisomy 1 (8.1%), followed by +8 (4.8%). In post-PV MF patients, the most common abnormal karyotypes were -17 (5.0%) and -5/5q- (5.0%).

We analyzed the impact of abnormal karyotypes on the survival prognosis of MF patients. In MF patients (including those with overt PMF, post-ET MF, and post-PV MF), abnormal karyotypes were associated with significantly shortened overall survival (OS) compared to normal karyotypes (P&lt;0.0001, P=0.0483, P&lt;0.0001). In overt PMF and post-ET MF patients, both monosomal karyotypes and complex karyotypes were associated with significantly shortened OS compared to normal karyotypes (P&lt;0.0001, P&lt;0.0001). In overt PMF patients, the isolated +8 karyotype was associated with shortened OS compared to normal karyotypes (P=0.0001). In post-ET MF patients with the +8 karyotype (3 cases), all with additional abnormal karyotypes, OS was significantly shortened compared to those with normal karyotypes (P=0.0010). In overt PMF patients with the 1q+ karyotype (7 cases), all with additional abnormal karyotypes, OS was significantly shortened compared to those with normal karyotypes (P=0.0002). In post-ET MF patients with an isolated 1q+ karyotype, OS was significantly shortened compared to those with normal karyotypes (P=0.0007). Analysis of the impact of other common abnormal karyotypes on the survival prognosis of overt PMF patients revealed that -13/13q-, -7/7q-, -11/11q-, +9, -12/12q-, -17, der(6), -5/5q-, and +19 abnormal karyotypes were associated with significantly shortened OS compared to normal karyotypes (P=0.0191, P＜0.0001, P=0.0030, P=0.0102, P=0.0014, P＜0.0001, P=0.0023, P＜0.0001, P=0.0021).

In conclusion, abnormal karyotypes, complex karyotypes, and monosomal karyotypes were adverse prognostic factors in MF patients. Aberrations such as +8, -13/13q-, -7/7q-, -11/11q-, +9, -12/12q-, -17, der(6), -5/5q-, and +19 all indicated poor prognosis in overt PMF patients, and translocations/duplications of chromosomes 1 and +8 were associated with poor prognosis in post-ET MF patients.

Acknowledgement: This research was funded by the Key R&D Program of Zhejiang, No. 2022C03137; Public Technology Application Research Program of Zhejiang, China, No. LGF21H080003; Zhejiang Medical Association Clinical Medical Research special fund project, No. 2022ZYC-D09.

*Correspondence to: Jian Huang, M.D., Ph.D., Department of Hematology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang, China. E-mail: househuang@zju.edu.cn