Objective:To explore differences in the efficacy and safety of ruxolitinib in patients with myelofibrosis by age and to identify prognostic factors by analyzing clinical features and characteristics of chromosomes and gene mutations.Methods:This study retrospectively analyzed 188 patients with myelofibrosis who received ruxolitinib in the Department of Hematology, Qilu Hospital, Shandong University from January 1, 2017, to July 1, 2024. According to age at diagnosis, the patients were divided into the middle-aged group (≤55 years), young elderly group (56-65 years), and elderly group (>65 years). Clinical features, the characteristics of chromosomes and gene mutations, and the efficacy and safety of ruxolitinib treatment were compared across the three age groups. Independent factors influencing overall survival were identified through Cox proportional risk regression analysis.Results:Before treatment, the elderly group had more underlying comorbidities, a heavier symptom burden, higher leukocyte count, higher proportion and frequency of JAK2 mutations, and lower proportion of CALR mutations. The incidence of nondriver gene mutations was significantly higher in the young elderly group. After ruxolitinib treatment, the degree of reduction in spleen size did not differ significantly among the three groups. The length of the palpable spleen below the left costal margin reduced by more than 50% from baseline in 50.9% (27/53) of the patients in the middle-aged group, 43.5% (27/62) in the young elderly group, and 45.5% (20/44) in the elderly group ( P=0.720). No significant difference was observed among the three groups in the degree of reduction in Myeloproliferative Neoplasm Symptom Assessment Form (10-item version) score ( P=0.153), with a reduction in total symptom score by more than 50% achieved by 54.0% (27/50), 60.3% (41/68), and 66.7% (34/51) of the patients from the three groups, respectively ( P=0.429). The most common hematological adverse events were anemia and thrombocytopenia, while the most common nonhematological adverse events were electrolyte disturbance, elevated transaminase activity, and pulmonary infection. Multivariate analysis indicated that in ruxolitinib-treated patients with myelofibrosis, poor overall survival was independently predicted by increased age, reduced hemoglobin, percentage of bone marrow blasts ≥ 1%, absence of JAK2 mutations, chromosomal abnormalities, ≥2 high-molecular-risk mutations, and TP53 mutations. Conclusions:Patients with myelofibrosis stratified by age exhibited heterogeneous clinical features and gene mutation profiles but similar efficacy of ruxolitinib treatment and occurrence of adverse events.

Objective:To explore differences in the efficacy and safety of ruxolitinib in patients with myelofibrosis by age and to identify prognostic factors by analyzing clinical features and characteristics of chromosomes and gene mutations.Methods:This study retrospectively analyzed 188 patients with myelofibrosis who received ruxolitinib in the Department of Hematology, Qilu Hospital, Shandong University from January 1, 2017, to July 1, 2024. According to age at diagnosis, the patients were divided into the middle-aged group (≤55 years), young elderly group (56-65 years), and elderly group (>65 years). Clinical features, the characteristics of chromosomes and gene mutations, and the efficacy and safety of ruxolitinib treatment were compared across the three age groups. Independent factors influencing overall survival were identified through Cox proportional risk regression analysis.Results:Before treatment, the elderly group had more underlying comorbidities, a heavier symptom burden, higher leukocyte count, higher proportion and frequency of JAK2 mutations, and lower proportion of CALR mutations. The incidence of nondriver gene mutations was significantly higher in the young elderly group. After ruxolitinib treatment, the degree of reduction in spleen size did not differ significantly among the three groups. The length of the palpable spleen below the left costal margin reduced by more than 50% from baseline in 50.9% (27/53) of the patients in the middle-aged group, 43.5% (27/62) in the young elderly group, and 45.5% (20/44) in the elderly group ( P=0.720). No significant difference was observed among the three groups in the degree of reduction in Myeloproliferative Neoplasm Symptom Assessment Form (10-item version) score ( P=0.153), with a reduction in total symptom score by more than 50% achieved by 54.0% (27/50), 60.3% (41/68), and 66.7% (34/51) of the patients from the three groups, respectively ( P=0.429). The most common hematological adverse events were anemia and thrombocytopenia, while the most common nonhematological adverse events were electrolyte disturbance, elevated transaminase activity, and pulmonary infection. Multivariate analysis indicated that in ruxolitinib-treated patients with myelofibrosis, poor overall survival was independently predicted by increased age, reduced hemoglobin, percentage of bone marrow blasts ≥ 1%, absence of JAK2 mutations, chromosomal abnormalities, ≥2 high-molecular-risk mutations, and TP53 mutations. Conclusions:Patients with myelofibrosis stratified by age exhibited heterogeneous clinical features and gene mutation profiles but similar efficacy of ruxolitinib treatment and occurrence of adverse events.

AIM: To investigate the role of Forkhead box M 1 ( FoxM1 ) and B-cell leukemia/lymphoma-2 (Bcl-2) in the pathogenesis of acute myeloid leukemia (AML).METHODS:RT-qPCR and immunofluorescence analysis were used to determine the expression of FoxM 1 at mRNA and protein levels in AML-de novo patients, AML-complete re-mission (CR) patients, AML-refractoriness and relapse (RR) patients and healthy controls.HL60 cells and K562 cells were transfected with FoxM1 siRNA.The cell proliferation was detected by cell proliferation assay and colony formation as-say on soft agar, and the cell apoptosis was determined by flow cytometry .The expression of FoxM1 and Bcl-2 at mRNA and protein levels was detected by RT-qPCR and Western blotting .The activity of bcl-2 promoter was examined by lucifer-ase reporter assay with FoxM1 targetting.RESULTS:FoxM1 expression level in the AML-de novo patients was significant-ly higher than that in the healthy controls .As compared with the AML-de novo patients, FoxM1 expression in the AML-CR patients was reduced , and the FoxM1 expression level was the highest in the AML-RR patients .FoxM1 expression was in-hibited in the HL60 cells and K562 cells transfected with FoxM1 siRNA.Transfection with FoxM1 siRNA in the HL60 cells and K562 cells inhibited the proliferation as compared with NC siRNA transfection , and impaired the colony formation abili-ty.On the contrary , transfection with FoxM1 siRNA promoted the cell apoptosis .FoxM1 regulated bcl-2 expression posi-tively.CONCLUSION:FoxM1 promotes the development of AML by regulating bcl-2 expression.Silencing of FoxM1 ex-pression suppresses cell proliferation and promotes cell apoptosis .FoxM1 is a potential target for AML treatment .

AIM:To study whether inhibition of forkhead box protein M1(FoxM1) sensitizes leukemia K562 cells to homoharringtonine ( HHT ) .METHODS: K562 cells were incubated with HHT at different concentrations ( 0μmol/L, 0.015 μmol/L, 0.030μmol/L and 0.045μmol/L) for different time (0 h, 24 h, 48 h and 72 h).The mRNA and protein levels of FoxM1 were detected by real-time PCR and Western blot.FoxM1 siRNA was transfected into K562 cells with 0.015μmol/L HHT after 6 h.After 72 h incubation, the cell proliferation was detected by cell counting and soft agar assay, and the proportion of apoptotic K562 cells was determined by flow cytometry.The expression of c-Myc and Sp1 were detected by real-time PCR and Western blot.RESULTS:FoxM1 expression was reduced time-dependently and dose-dependently, suggesting that HHT mediated the downregulation of FoxM1 in K562 cells.In K562 cells, treatment with FoxM1 siRNA and HHT inhibited the cell proliferation and promoted the apoptosis significantly.Therefore, inhibition of FoxM1 sensitized leukemia K562 cells to HHT.The expression of c-Myc and Sp1 was positively regulated by FoxM1. CONCLUSION:HHT inhibits Forkhead box protein M1 expression in K562 cells.Inhibition of FoxM1 sensitizes K562 cells to HHT.