| ObjectiveTo analyse systematically the clinical and laboratory features of Philadelphia chromosome negative myeloproliferative neoplasms(MPNs) patients in our laboratory, comparing with the previous studies of Western countries and other regions of China, and to reveal the unique features of Ph-MPNs patients in our center.MethodsThe clinical information of 1648 Ph-MPNs patients from 2009 to 2015 was collected to analyse the mutations of driver genes of MPNs patients, and the clinical characteristics.Results1. General features of 1648 patients with Ph-MPNs: disease distribution: there are patients with polycythemia vera(PV) 508 cases(30.83%), patients with essential thrombocythemia(ET) 1049 cases(63.65%), 91 patients with primary myelofibrosis(PMF)(5.52%). Age and Sex: In our patient cohort, first onset age of MPNs patient can at any age, predominantly at the age of 40-79 years old. The median onset age was 60(3-95 years old). Male: Female was 1:1.09.2. The mutations of driver genes of 1648 patients with Ph-MPNs:(1) The JAK2V617 F mutation was found in 1364 patients(82.8%), 471 patients(93%)of 508 PV patients, 819 patients(78%)of 1049 ET patients and 74 patients(82%)of 91 PMF patients, respectively;(2) the JAK2 exon12 mutations were found in nine patients(1.7%)of 508 PV patients, the total mutation rate was 0.5%, none was found in ET or PMF patients;(3) the CALR mutations were found in 143 patients(8.7%), 132 patients(13%)of 1049 ET patients and 11 patients(12%)of 91 PMF patients, respectively, none was found in PV patients;(4) the MPL mutations were found in 10 patients(0.6%), 9 patients(1%)of 1049 ET patients and 1 patients(1%)of 91 PMF patients, respectively, none was found in PV patients. The co-occurrence of any two kinds of driver gene mutations was not detected by direct sequencing.3.The relevance of driver gene mutations and clinical characteristics of 1648 patients with Ph-MPNs: In our study, the median onset age of patients with JAK2V617 F was significant higher than patients with JAK2 exon12 mutation or without mutations(P<0.001), which was similar with patients with CALR or MPL mutation. Compared with patients with CALR mutation or without mutations, patients with JAK2V617 F had higher white blood cell count and higher hemoglobin level(differences are statistically significant), but compared with patients with MPL mutations, only high white blood cell count was statistically significant(P = 0.013). The platelet count of patients with CALR mutations was significantly higher than patients with JAK2V617F(P <0.001).4. The relevance of driver gene mutations and chromosome abnormalities of 1648 patients with Ph-MPNs: Karyotype analysis were conducted in 1160 patients with MPNs, the rates of karyotype abnormality of patients with and without CALR gene mutations were 9.8%(8/82) and 7.4%(80/1078),(P = 0.441); the rates of karyotype abnormality of patients with and without JAK2V617 F mutation were 7.7%(75/971) and 6.9%(13/189)(P = 0.688). The incidence of karyotype abnormality of patients with CALR was higher than patients with JAK2V617F(9.8%: 7.7%), but no statistically significant difference was found(P = 0.512). The karyotype analysis of 7 cases of JAK2 exon12 mutation and 6 patients with MPL gene mutations revealed normal karyotype.Conclusions(1) In our patient cohort, first onset age of MPNs patient can at any age, predominantly at the age of 40-79 years old, which was consistent with the previous studies of western countries.(2) The driver gene mutation spectrum of our center Ph-MPNs patients was consistent with previous reports, but the total mutation rate of CALR and MPL mutation was lower than the previous studies of western countries; different subtypes of MPNs had different types and frequencies of driver gene mutations, and, different driver gene mutations lead to unique clinical phenotype; the incidence of karyotype abnormality of patients with driver gene mutations was higher than patients without mutations, but there were no statistically significant difference.ObjectiveThe study analysed the clinical information of 1648 Philadelphia chromosome negative myeloproliferative neoplasms patients diagnosed in our center from 2009 to 2015, 9 cases with abnormal karyotype of + 9 patients as the research objects and 65 patients with normal karyotype as controls were studied, to analyse JAK2V617 F allele burden in patients with myeloproliferative neoplasms carrying a Trisomy 9 and its relationship with clinical phenotypes.MethodsThe clinical information of 1648 Ph-MPNs patients from 2009 to 2015 was collected and all patients were classified according to the WHO(2008) criterion. 9 cases with abnormal karyotype of + 9 as the research objects(including 3 cases with PV, 5 patients with ET and 1 case with PMF) and 65 patients with normal karyotype as controls(including 21 cases with PV and 44 patients with ET) were studied, to analyse JAK2V617 F allele burden in patients with myeloproliferative neoplasms carrying a Trisomy 9 and its relationship with clinical phenotypes.There are all JAK2V617 F mutation positive.Results(1) In our patient cohort, the incidence of +9 abnormal karyotype in MPNs patients was 10.2%(9/88), in patients with PV was 17.6%(3/17), in patients with ET was 11.1%(6/54); in patients with PMF was 5.9%(1/17). The most common abnormal of ET and PV patients was +9, while patients with PMF was the complex karyotype.(2) The analysis of JAK2V617 F mutation allele burden: Compared with the normal karyotype group, patients with +9 had higher JAK2V617 F allele burden. In this study, we found that the difference was more significant in patients with ET, in the PV patients, the two groups showed no obvious difference.(3) In the terms of clinical characteristics, peripheral blood leukocyte count of patients with +9 was significantly higher than the normal karyotype group, P value was statistically significant, while the median onset age, sex, splenomegaly, and the incidence of thrombotic events between the two groups had no significant difference.(4) We took the overall median JAK2V617 F mutation allele burden(31.1%) as a standard of screening, further explored the correlation between the abnormal karyotype of +9 and clinical features in ET and PV patients with high burden. The study found that the two groups showed no obvious difference.ConclusionsIn our study, patients with +9 had higher JAK2V617 F allele burden, higher peripheral blood leukocyte count, while no significant difference was found in aspects of the median onset age, sex, concentration of hemoglobin, platelet count, splenomegaly, and thrombotic events, which was consistent with previous research. Meanwhile, we found that the difference was more significant in patients with ET, in the PV patients, the two groups showed no obvious difference. In the patients cohort of high JAK2V617 F mutation allele burden, there is no significant difference of clinical parameters between the two groups. +9, as a frequent cytogenetic abnormality in both PV and ET, might be an alternative mechanism of increasing JAK2V617 F dosage to influence clinical phenotype. |
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