| BackgroundMyelofibrosis(MF)is a BCR-ABL-negative myeloproliferative tumor(MPN).It can be a primary disease or secondary to other diseases.The pathogenesis of myelofibrosis is still unclear.About 50%of patients with bone marrow fibrosis have JAK2V617F point mutations.Therefore,the most studied pathway for bone marrow fibrosis is the JAK-STAT pathway,but the application of JAK inhibitors cannot effectively reverse the course of bone marrow fibrosis.Studies are looking for other signaling pathways in bone marrow fibrosis.PurposeRetrospective analysis of patients diagnosed with primary or secondary myelofibrosis in our hospital in the past 3 years,and analyze the clinical characteristics of primary and secondary myelofibrosis;and through the GEO database of myelofibrosis Enrichment analysis of gene and gene expression profiles,to explore other signaling pathways other than the JAK-STAT pathway,and guide the direction of clinical diagnosis.MethodsThe study subjects were 43 patients diagnosed with primary or secondary myelofibrosis in our hospital from August 2015 to December 2018.The clinical diagnosis data were collected,including gender,age,white blood cell count,red blood cell count,Hemoglobin level,platelet count,spleen size,bone marrow biopsy results,peripheral blood smears,genetic testing and other clinical laboratory test results;and gene expression profiles for bone marrow fibrosis GSE26049,GSE84638 downloaded from the free public database Gene Expression Omnibus(GEO),GSE124281.Gene set enrichment analysis was performed by Broad Institute website GSEA software.We mainly analyze the HALLMARK gene set.Gene sets with P<0.05 and False Discovery Rate(FDR)<0.25 in GSEA were taken as significant difference enrichment gene sets.Statistical methods Data were processed using SPSS 25.0 statistical software.Obey the normal distribution measurement data using independent sample t test analysis data,P<0.05 as the difference is statistically significant.Result1.A total of 43 patients with myelofibrosis were included,including 25 patients with primary myelofibrosis and 18 patients with secondary myelofibrosis.The age range was47-79 years,and the average age was 64 years.43 patients There were abnormalities in hemogram,and in patients with PMF,mild anemia was common;19 patients(76%)had abnormal white blood cells,with an average of 13.0(2.7-37.9)×10~9/L;20 patients(80%)had abnormal hemoglobin.The average value was 95.0(42.0-183.0)g/L;18 patients(72%)had platelet abnormalities,with an average value of 276.6(5.0-799.0)×10~9/L,of which 11 patients(44%)had thrombocytosis,and Seven patients(28%).The spleen enlargement was found in all 25 patients with PMF.The average spleen size was 67.5(44-98)mm.Patients with primary bone marrow fibrosis are at risk for thrombosis,which may be related to thrombocytosis;2.Among the patients with secondary myelofibrosis,the clinical manifestations are closely related to the primary disease.Therefore,the clinical values of patients with secondary myelofibrosis have a large deviation,and 18 patients(43%)have secondary myelofibrosis.,The age range is 47-77 years,the average age is 64 years old.Sixteen(89%)patients had abnormal blood routines,of which 10(56%)had abnormal white blood cells,with an average of 18.9(2.1-221.2)×10~9/L;15(83%)had abnormal hemoglobin,with an average of 97.1(36.0-210.0)g/L;13 patients(72%)had abnormal platelets,with an average of 366.2(7.0-1733.0)×10~9/L,of which 7(39%)had thrombocytosis,and patients with thrombocytopenia had 5 cases(28%).Eleven(61%)patients with SMF had splenomegaly,and the average spleen size was 44.9±13.0(29.0-77.0)mm.Seven(39%)patients had normal spleen size.However,39%of patients with thrombocytosis are observed,so the risk of thrombosis in patients with secondary myelofibrosis may be related to this;3.Patients with primary myelofibrosis and secondary myelofibrosis had enlarged spleens.The average spleen size of patients with primary myelofibrosis was 67.5mm,while the incidence of splenomegaly was only 61%in patients with secondary myelofibrosis.The spleen size was normal in the other 39%of patients.The spleen size of patients with secondary myelofibrosis was 44.9±13.0mm.The spleen of patients with primary myelofibrosis was significantly larger than that of patients with secondary myelofibrosis(P<0.0001);4.By analyzing the gene profiles of the three gene databases,the HALLMARK gene set positively related to bone marrow fibrosis has a reactive oxygen species(ROS)pathway,and epithelial-mesenchymal transition is abnormally prominent,which may become the next target for primary bone marrow fibrosis.ConclusionHematology was abnormal in all patients with bone marrow fibrosis,and the incidence of splenomegaly and spleen size of primary bone marrow fibrosis were significantly higher than those of secondary bone marrow fibrosis.Combined with clinical data and genomic enrichment analysis,in addition to inhibitors of the JAK-STAT signaling pathway,consider the reactive oxygen species(ROS)pathway,epithelial-mesenchymal transition,G2M checkpoints,MTOR signaling pathway,angiogenesis,KRAS,Signaling pathways such as NOTCH and MYC may also be developed for the treatment of primary bone marrow fibrosis.Combined with current related studies,epithelial-mesenchymal transition plays a very important role in the process of fibrosis and may become the next molecular mechanism of bone marrow.direction. |
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