Extramedullary hematopoiesis denotes blood cell production in hematopoietic tissue other than bone marrow. Myeloproliferative disorders, including myelofibrosis, polycythemia vera, essential thrombocythemia and chronic myelogenous leukemia (CML) are the most common cause of extramedullary hematopoiesis. Extramedullary hematopoiesis most commonly occurs in the spleen, liver and lymph nodes but has been reported in almost all sites of the body. Usually extramedullary hematopoiesis has been reported to involve liver, without forming a liver mass in a patient with CML. We report a patient with CML who had extramedullary hematopoiesis presenting as a liver mass established by ultrasound-guided biopsy.
Biopsy ; Blood Cells ; Bone Marrow ; Hematopoiesis, Extramedullary* ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive* ; Liver* ; Lymph Nodes ; Myeloproliferative Disorders ; Polycythemia Vera ; Primary Myelofibrosis ; Spleen ; Thrombocythemia, Essential

BACKGROUND: A soluble form of interleukin-2 receptor (sIL-2R) is released from activated T cells. Serum sIL-2R levels are elevated in some hematological malignancies and could be used to assess disease activity and prognosis. MATERIAL AND METHODS: To define clinical usefulness and significance as a marker predicting disease progress in chronic myeloproliferative disorders, the serum levels of sIL-2R were measured in 40 cases of chronic myelogenous leukemia (CML; 25 chronic phase, 7 accelerating phase, 8 blastic phase), 3 cases of polycythemia vera (PV), 5 cases of essential thrombocythemia (ET) and 4 cases of idiopathic myelofibrosis (MF) and in 37 cases of healthy subjects using sandwich enzyme immunoassay. RESULTS: Serum sIL-2R levels in the patients of CML, PV, ET, and MF were higher compared with the normal healthy controls. In CML, serum sIL-2R levels in the patients of blastic and accelerating phases were significantly higher than those of chronic phase. In CML of chronic phase, serum sIL-2R levels at diagnosis were related to WBC count but not to other clinical and hematologic paramaters. The leukemic cells of one patient with lymphoblastic phase of CML expressed IL-2R (CD25). Among 4 patients of CML with sIL-2R levels above 2,000U/mL at diagnosis, transformation to blastic crisis was noted in 3 patients and 2 patients died within 1 year after diagnosis. But among 11 patients of CML with sIL-2R levels below 2,000U/mL at diagnosis, only 2 patients experienced blastic crisis and died within 1 year after diagnosis. CONCLUSION: This study indicated that serum sIL-2R levels were high in chronic myeloproliferative disorders, and that increasing levels of serum sIL-2R might be useful to predict disease progress. Further studies including more patients and longer follow-up may substantiate serum sIL-2R as a prognostic indicator in CML.
Diagnosis ; Hematologic Neoplasms ; Humans ; Immunoenzyme Techniques ; Interleukin-2* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Myeloproliferative Disorders* ; Polycythemia Vera ; Primary Myelofibrosis ; Prognosis ; T-Lymphocytes ; Thrombocythemia, Essential

The classic BCR-ABL negative myeloproliferative neoplasm (MPN) comprise polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). These three disorders are characterized by stem cell-derived clonal myeloproliferation and presence of somatic mutations. The WHO diagnostic criteria for the classic BCR-ABL negative MPN has been revised in the 2008 edition by incorporating new information about their molecular pathogenesis. Robust prognostic system for PMF has already done, and those for PV and ET are under discussion. Treatment with novel drugs is promising, and allo-stem cell transplantation (allo-ASCT) is the only curative treatment for myelofibrosis, however, the patient selection and management before transplant have been discussed for a long time.
Fusion Proteins, bcr-abl ; Humans ; Myeloproliferative Disorders ; Polycythemia Vera ; Primary Myelofibrosis ; Prognosis ; Thrombocythemia, Essential ; World Health Organization

The World Health Organization (WHO) Classification of Tumors of Haematopoietic and Lymphoid Tissues was recently published in a revised fourth edition. The categories of myeloproliferative neoplasms (MPNs) have not significantly changed since the 2008 fourth edition of the classification; however, newly discovered mutations including CALR and CSF3R and improved characterizations and standardizations of morphological features of some entities, particularly BCR-ABL1-negative MPNs, have impacted the diagnostic criteria of disease entities, increasing the reliability and reproducibility of diagnoses. The 2017 revised edition attempts to incorporate new clinical, prognostic, morphologic, and genetic data that have emerged since the last edition. This article reviews the major changes in the classification and their rationale for MPN classification within the revised 2017 WHO system.
Classification ; Diagnosis ; Global Health* ; Lymphoid Tissue ; Myeloproliferative Disorders ; Polycythemia Vera ; Primary Myelofibrosis ; Thrombocythemia, Essential ; World Health Organization*

BACKGROUND: Thrombocytosis can result in life-threatening thrombotic or hemorrhagic events. Anagrelide acts exclusively on megakaryocytes and has been reported as an useful agent in controlling thromobocytosis associated with chronic myeloproliferative disorders. METHODS: Seven patients with essential thrombocythemia and three with chronic myelogenous leukemia were enrolled and early responses and adverse effects of anagrelide were retrospectively analyzed. The drug was started with a dose of 2 mg/day with increases of 0.5 mg/day every 5~7 days as needed. RESULTS: Anagrelide in starting doses of 2 mg/day reduced the platelet count by 50%, or to less than 600,000/mm3, for at least 28 days in 7 of the 9 (78%) evaluable patients. Adverse effects of the drug were observed in 5 patients and generally well tolerated; headache in 4, gastrointestinal troubles in 2, palpitations and chest tightness in 1, and tinnitus in 1. Changes in hemoglobin or white blood cell counts in peripheral blood were minimal and tolerable. CONCLUSION: The present study shows that anagrelide is a useful platelet-lowering agent in whom hydroxyurea or interferon has failed. Long-term efficacy and adverse effects of the drug remain to be determined.
Headache ; Humans ; Hydroxyurea ; Interferons ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Leukocyte Count ; Megakaryocytes ; Myeloproliferative Disorders ; Platelet Count ; Retrospective Studies ; Thorax ; Thrombocythemia, Essential ; Thrombocytosis* ; Tinnitus

OBJECTIVETo detect the JAK2, CALR and MPL gene mutations in patients with BCR/ABL1 negative chronic myeloproliferative diseases（BCR/ABL1-CMPD）and to evaluate their diagnostic value.

METHODSTwo hundred and eight cases of BCR/ABL1-CMPD comprising of 146 cases of essential thrombocythemia（ET）, 37 cases of polycythemia vera（PV）and 25 cases of primary myelofibrosis（PMF）from March 2012 to December 2015 were enrolled in the BCR/ABL1-CMPD, while 124 cases of secondary thrombocythemia and 73 cases of secondary polycythemia were enrolled in the control group. The genomic DNA and total RNA Were isolated from bone marrow or peripheral blood, then the exons 12 to 20 of JAK2 gene, exon 10 of MPL gene and exons 3 to 9 of CALR gene were analyzed by using DNA sequencing.

RESULTSamong 146 ET patients, the JAK2, CALR or MPL mutations were found in: 138 cases（94.5%）including 86 cases with JAK2V617F mutation（58.9%）and 2 cases（1.4%）with exon 12 of JAK2 mutations. CALR mutations were detected in 41 cases（28.1%）, among them type 1（c.1092_1143del）in 22 cases, type 2（c.1154_1155insTTGTC）in 11 cases, and type 5（c. 1091_1142del）, type 8（c.1104_1137del）, type 41(c.1107_1137del）, type 42(c.1125_1125del）in one case respectively. In addition, 4 cases were detected withother mutations of the CALR gene（c.1107_1115del, c.1111_1144 del, c.1101 A>C, c.1112_1117del）. Moreover, 9 cases harbored MPL mutations（6.2%）. Secondly, 31 patients were detected with JAK2V617F mutation（83.8%）in 37 cases of PV, and JAK2 exon 12 mutations were found in 2 cases（5.4%）. Besides, CALR mutations were detected in 2 cases（5.4%）, including 1 case of type I, the other of novel mutation of CALR. Thirdly, 19 in 25 cases of PMF were detected with JAK2V617F mutation（76%）, 2 cases with CALR mutations（8%）. 4 patients（16%）, JAK2, CALR or MPL mutations were not detected, but among them 3 cases were found harboring other genetic abnormalities. Fourthly, no mutations of JAK2, MPL and CALR genes were detected in 124 patients with secondary thrombocytosis and 73 cases with secondary polycythemia.

CONCLUSIONCombined detection of JAK2, CALR and MPL gene mutations can cover the vast majority of patients with BCR/ABL1-negative myeloproliferative neoplasms. For higher frequencies of the mutations of CALR in ET patients, CALR mutation can be used as a new diagnostic marker in ET patients with JAK2 and MPL wild type.

Calreticulin ; Humans ; Janus Kinase 2 ; Mutation ; Myeloproliferative Disorders ; Polycythemia Vera ; Receptors, Thrombopoietin ; Thrombocythemia, Essential

No abstract available.
Female ; Fusion Proteins, bcr-abl/*genetics ; Humans ; Male ; Middle Aged ; Mutation ; Myeloproliferative Disorders/*genetics ; Polycythemia Vera/genetics ; Primary Myelofibrosis/genetics ; Proteins/*genetics ; Thrombocythemia, Essential/genetics

Classical BCR/ABL fusion gene negative myeloproliferative neoplasms (MPN), including polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF), are clonal hematopoietic malignancies sharing in common origin in a multipotential hematopoietic stem cell. The phenotypic variability of the three entities can not be elucidated by JAK2V617F mutation only. Recent discoveries indicated that JAK2V617F allele burden, other mutated genes (such as TET2, ASXL1) and inherited predisposition can play roles in the complicated pathogenesis of MPN, which are summarized in this review.
Bone Marrow Neoplasms ; genetics ; Genetic Predisposition to Disease ; Humans ; Janus Kinase 2 ; genetics ; Mutation ; Myeloproliferative Disorders ; genetics ; Polycythemia Vera ; genetics ; Primary Myelofibrosis ; genetics ; Thrombocythemia, Essential ; genetics

OBJECTIVETo detect JAK2 V617F mutation burden and its clinical implications in patients with myeloproliferative neoplasm (MPN).

METHODSJAK2 V617F mutation burden were detected by using MGB Taqman probes and its clinical significance were retrospectively studied in 415 MPN patients.

RESULTSJAK2 V617F was found in 56.9% of all patients [83.5% in polycythemia vera (PV), 55.9% in essential thrombocythemia (ET), 41.9% in primary myelofibrosis (PMF) and 64.7% in MPN-unclassifiable)]. The majority of patients carried heterozygous JAK2 V617F mutation and homozygote was found only in 12 cases (4 in PV, 4 in MPN-U, 2 in PMF, 1 in ET, and 1 in chronic neutrophilic leukemia). Most patients (68.8%) were lower mutation burden (mutation burden<50%), but PV had the highest burden, the moderate burden in PMF and the least in ET. The patient's age and WBC count were significantly correlated with higher mutation burden in PV. WBC count was significantly related to higher mutation burden in ET. WBC count, Hb level and the platelet count were significantly related to higher mutation burden in PMF.

CONCLUSIONThe mutation burden of JAK2 V617F from high to low was PV, ET and PMF. The majority of JAK2 V617F mutation was heterozygous. JAK2 V617F mutation burden was positively correlated with age, WBC, Hb and platelet counts.

Homozygote ; Humans ; Janus Kinase 2 ; Leukocyte Count ; Mutation ; Myeloproliferative Disorders ; Platelet Count ; Polycythemia Vera ; Retrospective Studies ; Thrombocythemia, Essential

Essential thrombocythemia is one type of the related chronic myeloproliferative disorders that also include poly-cythemia vera, chronic myelogenous leukemia, and idiopathic myelofibrosis. It is a rare disorder of unknown origin characterized by thrombocytosis, excessive megakaryocytes, hemorrhage, and thrombotic complication. Several cases of ischemic stroke in essential thrombocythemia have been reported, but cerebral infarction combined with cerebral hemorrhage has been very rare and has not been reported in Korea. We report a case of cerebral infarction and chronic subdural hematoma in a pateint with essential thrombocythemia. A 59-year-old woman with essential thrombocythemia was admitted with mild left hemiparesis that developed 3 days prior. She had a history of minor trauma 15 days prior. A brain MRI showed an infarction in the right temporal lobe and a chronic subdural hematoma in the right frontoparietal area. A cerebral angiography revealed an occlusion of the M2 portion of the right middle cerebral artery.
Brain ; Cerebral Angiography ; Cerebral Hemorrhage ; Cerebral Infarction* ; Female ; Hematoma, Subdural, Chronic* ; Hemorrhage ; Humans ; Infarction ; Korea ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Magnetic Resonance Imaging ; Megakaryocytes ; Middle Aged ; Middle Cerebral Artery ; Myeloproliferative Disorders ; Paresis ; Primary Myelofibrosis ; Stroke ; Temporal Lobe ; Thrombocythemia, Essential* ; Thrombocytosis