JAK2 V617F, MPL W515L and JAK2 Exon 12 Mutations in Chinese Patients with Primary Myelofibrosis

Objective： JAK2 V617F, MPL W515L and JAK2 exon 12 mutations are novel acquired mutations that induce constitutive cytokine-independent activation of the JAK-STAT pathway in myeloproliferative disorders （MPD）. The discovery of these mutations provides novel mechanism for activation of signal transduction in hematopoietic malignancies. This research was to investigate their prevalence in Chinese patients with primary myelofibrosis （PMF）. Methods： We introduced allele-specific PCR （AS-PCR） combined with sequence analysis to simultaneously screen JAK2 V617F, MPL W515L and JAK2 exon 12 mutations in 30 patients with PMF. Results： Fifteen PMF patients （50.0%） carried JAK2 V617F mutation, and only two JAK2 V617F-negative patients （6.7%） harbored MPL W515L mutation. None had JAK2 exon 12 mutations. Furthermore, these three mutations were not detected in 50 healthy controls. Conclusion： MPL W515L and JAK2 V617F mutations existed in PMF patients but JAK2 exon 12 mutations not. JAK2 V617F and MPL W515L and mutations might contribute to the primary molecular pathogenesis in patients with PMF.

Primary myelofibrosis with concurrent CALR and MPL mutations:A case report

BACKGROUND Primary myelofibrosis(PMF)is a myeloproliferative neoplasm(MPN)characterized by recurrent mutations in the JAK2,CALR,and MPL genes.The CALR and MPL co-mutation is very rare.To our knowledge,no more than five cases have been reported.Here,we report a case of PMF in which a CALR and MPL co-mutation was detected by next-generation sequencing(NGS)technology,and a literature review was performed.CASE SUMMARY A 73-year-old woman was admitted to our hospital in 2018 due to abdominal distension.The patient had splenomegaly,lymphadenopathy,leukopenia,anemia,and immature granulocytes in peripheral blood.There were dacrocytes and atypical megakaryocytes in bone marrow,and megakaryocytic proliferation was very active,accompanied by reticulin fibrosis grade 2.By NGS analysis of the bone marrow sample,we detected mutations in CALR,MPL,and PIK3RI,while JAK2 V617F and BCR-ABL were negative.Therefore,the patient was diagnosed with PMF and received oral ruxolitinib.However,the spleen and hematologic responses were poor.We review the literature,analyze previous reports of the mutation sites in our patient and differences between our patient and other reported cases of co-mutated CALR and MPL genes,and discuss the reason why the CALR and MPL co-mutations are rare and possible mechanisms and their impact on the prognosis of patients.CONCLUSION CALR and MPL mutations can be concurrent in MPN,but they are rare.The use of NGS may help to identify more patients with co-mutated CALR and MPL genes.This will help to further explore the mechanism and its impact on these patients to develop appropriate treatment strategies.

Intestinal obstruction caused by extramedullary hematopoiesis and ascites in primary myelofibrosis

Primary myelofibrosis(PMF) is a clonal hematopoietic stem cell disorder. It is characterized by bone marrow fibrosis, extramedullary hematopoiesis with hepatosplenomegaly and leukoerythroblastosis in the peripheral blood. The main clinical manifestations of PMF are anemia, bleeding, hepatosplenomegaly, fatigue, and fever. Here we report a rare case of PMF with anemia, small bowel obstruction and ascites due to extramedullary hematopoiesis and portal hypertension. The diagnosis was difficult to establish before surgery and the differential diagnosis is discussed.

Turner syndrome with primary myelofibrosis,cirrhosis and ovarian cystic mass:A case report

BACKGROUND Turner syndrome(TS)with leukemia is a complicated clinical condition.The clinical course and outcome of these patients are poor,so the treatment and prognosis of TS with hematological malignancies deserve our attention.CASE SUMMARY Here,we report a case of a 20-year-old woman diagnosed with TS,primary myelofibrosis(PMF),cirrhosis,and an ovarian cystic mass.This is the first report on the coexistence of TS and PMF with the MPL and SH2B3 mutations.The patient was diagnosed with cirrhosis of unknown cause,splenomegaly and severe gastroesophageal varices.Additionally,an ovarian cystic mass caused the patient to appear pregnant.The patient was treated with the JAK2 inhibitor-ruxolitinib according to peripheral blood cells,although myelofibrosis was improved,the splenomegaly did not reduce.Moreover,hematemesis and melena occasionally occurred.CONCLUSION Ruxolitinib may clearly reduce splenomegaly.Though myelofibrosis was improved,cirrhosis and splenomegaly in this case continued to worsen.Effective treatment should be discussed.

Advances in the Study of High-Risk Gene Mutations for Primary Myelofibrosis

Primary myelofibrosis is a kind of MPNs due to clonal appreciation of hematopoietic stem cells. With the development of second-generation sequencing, high-risk mutation (HMR) genes such as ASXL1, EZH2, SRSF2, and IDH1/2 have been shown to be associated with disease prognosis and progression, and although allo-HSCT remains the only possible treatment for PMF, with the development of JAK inhibitors, there is an increasing interest in the study of inhibitors of these mutant loci.

Prognostic value of JAK2, MPL and CALR mutations in Chinese patients with primary myelofibrosis

Objective To evaluate the prognostic value of JAK2,MPL and CALR mutations in Chinese patients with primary myelofibrosis(PMF).Methods Four hundred and two Chinese patients with PMF were retrospectively analyzed.The Kaplan-Meier method,the Log-rank test,the likelihood ratio test and the Cox

Peritonitis in myelofibrosis:a cautionary tale

BACKGROUND: Primary myelofibrosis (PMF) is a myeloproliferative disorder characterized by bone marrow fibrosis. Extra-medullary hematopoiesis sometimes occurs even in the peritoneal cavity, apart from organs such as the liver, spleen, and lymph nodes. This may sometimes be complicated by spontaneous infection and complications. We report a rather unusual case of PMF, who presented as an emergency with spontaneous peritonitis to general surgery department and had a fulminant clinical course. METHOD: A clinical case note review was done and a literature search was undertaken. RESULTS: A rather unusual case of PMF, who presented as an emergency with spontaneous peritonitis to general surgery department. The patient underwent a laparotomy and had a fulminant clinical course. CONCLUSIONS: Peritonitis in myelofibrosis may have a number of causes. Clinicians need to be aware of them and provide conservative management prior to surgical treatment. (Hepatobiliary Pancreat Dis Int 2010; 9: 651-653)

Budd-Chiari syndrome in myeloproliferative neoplasms:A review of literature

Myeloproliferative neoplasms(MPNs)are defined as clonal disorders of the hematopoietic stem cell in which an exaggerated production of terminally differentiated myeloid cells occurs.Classical,Philadelphia-negative MPNs,i.e.,polycythemia vera,essential thrombocythemia and primary myelofibrosis,exhibit a propensity towards the development of thrombotic complications that can occur in unusual sites,e.g.,portal,splanchnic or hepatic veins,the placenta or cerebral sinuses.The pathogenesis of thrombotic events in MPNs is complex and requires an intricate mechanism involving endothelial injury,stasis,elevated leukocyte adhesion,integrins,neutrophil extracellular traps,somatic mutations(e.g.,the V617F point mutation in the JAK2 gene),microparticles,circulating endothelial cells,and other factors,to name a few.Herein,we review the available data on Budd-Chiari syndrome in Philadelphia-negative MPNs,with a particular focus on its epidemiology,pathogenesis,histopathology,risk factors,classification,clinical presentation,diagnosis,and management.