• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.923-926
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• 2016

The classic BCR-ABL1-negative myeloproliferative neoplasm is an operational sub-category of MPNs that includes polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The JAK2V617F mutation is found in ~ 95% of PV and 50-60% of ET or PMF. In most of the remaining JAK2V617F-negative PV cases, JAK2 exon 12 mutations are present. Amongst the JAK2V617F-negative ET or PMF 5-10% of patients carry mutations in the MPL gene. Prior to 2013, there was no specific molecular marker described in the remaining 30-40% ET and PMF. In December 2013, two research groups independently reported mutations in the gene CALR found specifically in ET (67-71%) and PMF (56-88%) but not in PV. Initially CALR mutations were reported mutually exclusive with JAK2 or MPL. However, co-occurrence of CALR mutations with JAK2V617F has been reported recently in a few MPN cases. Many studies have reported important diagnostic and prognostic significance of CALR mutations in ET and PMF patients and CALR mutation screening has been proposed to be incorporated into WHO diagnostic criteria for MPN. It is suggestive in diagnostic workup of MPN that CALR mutations should not be studied in MPN patients who carry JAK2 or MPL mutations. However JAK2V617F and CALR positive patients might have a different phenotype and clinical course, distinct from the JAK2-positive or CALR-positive subgroups and identification of the true frequency of these patients may be an important factor for defining the prognosis, risk factors and outcomes for MPN patients.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2219-2225
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• 2015

SHP1 negatively regulates the Janus kinase 2/signal transducer and activator of transcription (JAK2/STAT) signaling pathway, which is constitutively activated in myeloproliferative neoplasms (MPNs) and leukemia. Promoter hypermethylation resulting in epigenetic inactivation of SHP1 has been reported in myelomas, leukemias and other cancers. However, whether SHP1 hypermethylation occurs in MPNs, especially in Chinese patients, has remained unclear. Here, we report that aberrant hypermethylation of SHP1 was observed in several leukemic cell lines and bone marrow mononuclear cells from MPN patients. About 51 of 118 (43.2%) MPN patients including 23 of 50 (46%) polycythaemia vera patients, 20 of 50 (40%) essential thrombocythaemia and 8 of 18 (44.4%) idiopathic myelofibrosis showed hypermethylation by methylation-specific polymerase chain reaction. However, SHP1 methylation was not measured in 20 healthy volunteers. Hypermethylation of SHP1 was found in MPN patients with both positive (34/81, 42%) and negative (17/37, 45.9%) JAK2V617F mutation. The levels of SHP1 mRNA were significantly lower in hypermethylated samples than unmethylated samples, suggesting SHP1 may be epigenetically inactivated in MPN patients. Furthermore, treatment with 5-aza-2'-deoxycytidine (AZA) in K562 cells showing hypermethylation of SHP1 led to progressive demethylation of SHP1, with consequently increased reexpression of SHP1. Meanwhile, phosphorylated JAK2 and STAT3 were progressively reduced. Finally, AZA increased the expression of SHP1 in primary MPN cells with hypermethylation of SHP1. Therefore, our data suggest that epigenetic inactivation of SHP1 contributes to the constitutive activation of JAK2/STAT signaling. Restoration of SHP1 expression by AZA may contribute to clinical treatment for MPN patients.

• Korean journal of aerospace and environmental medicine
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• v.31 no.3
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• pp.82-83
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• 2021

Chronic myeloid leukemia (CML) is myeloproliferative neoplasm associated with a characteristic chromosomal translocation (bcr-abl) called Philadelphia chromosome which plays a key role in the pathogenesis. Approximately 85% of patients with CML are in the chronic phase at the time of diagnosis. During this phase, patients are well tolerated and have few symptoms. But untreated, over the course of several years progresses to an accelerated phase and ultimately to a blast crisis, the terminal phase. CML is largely treated with targeted drug therapy called tyrosine-kinase inhibitors (TKIs) which have led to dramatically improved long-term survival rates since 2001. These drugs became standard treatment of this disease and allow most patients to have much better quality of life when compared to the former chemotherapy drugs and the bone marrow transplantation. Imatinib (Gleevec or Glivec, Norvatis) was the first of these TKIs and found to inhibit the progression of CML in the majority of patients (65%-75%) sufficiently to achieve remission. Since the advent of imatinib, CML has become the first neoplasm in which a medical treatment can give to the patient a normal life expectancy.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8629-8631
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• 2016

Background: Primary idiopathic myelofibrosis (PMF) is a clonal Philadelphia chromosome-negative myeloproliferative neoplasm characterized by extramedullary hematopoiesis and marrow fibrosis. It is an uncommon hematopoietic malignancy which primarily affects elderly individuals. The rational of this study was to determine its clinico-epidemiological profile along with risk stratification in Pakistani patients. Materials and Methods: In this retrospective cross sectional study, 20 patients with idiopathic myelofibrosis were enrolled from January 2011 to December 2014. Data were analyzed with SPSS version 22. Results: The mean age was $57.9{\pm}16.5years$ with 70% of patients aged above 50. The male to female ratio was 3:1. Overall only 10% of patients were asymptomatic and the remainder presented with constitutional symptoms. In symptomatic patients, major complaints were weakness (80%), weight loss (75%), abdominal discomfort (60%), night sweats (13%), pruritus (5%) and cardiovascular accidents (5%). Physical examination revealed splenomegaly as a predominant finding detected in 17 patients (85%) with the mean splenic span of $22.2{\pm}2.04cm$. The mean hemoglobin was $9.16{\pm}2.52g/dl$ with the mean MCV of $88.2{\pm}19.7fl$. The total leukocyte count of $17.6{\pm}19.2{\times}10^9/l$ and platelets count were $346.5{\pm}321.9{\times}10^9/l$. Serum lactate dehydrogenase, serum creatinine and uric acid were $731.0{\pm}154.1$, $0.82{\pm}0.22$ and $4.76{\pm}1.33$ respectively. According to risk stratification, 35% were in high risk, 40% in intermediate risk and 25% in low risk groups. Conclusions: The majority of PMF patients were male and presented with constitutional symptoms in our setting. Risk stratification revealed predominance of advanced disease in our series.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7327-7330
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• 2015

Background: Essential thrombocythemia (ET) is a clonal hemopoietic stem cell myeloproliferative neoplasm characterized by persistent thrombocytosis along with megakaryocytic hyperplasia. In the last decade following the identification of an acquired JAK2 V617F mutation, there has been acceleration in our understanding of this disease. The rational of this study was to determine the mutational profile of JAK2 V617F in Pakistan patients with ET. Materials and Methods: In this retrospective cross sectional study, 21 patients with ET were enrolled from January 2011 to December 2014. Patients were diagnosed based on WHO criteria for essential thrombocythemia. Complete blood count was done on an automated hematology analyzer, while JAK2 V617F expression was evaluated by polymerase chain reaction. Results: The mean age was $56.7{\pm}19.0$ years (range 18-87) and the male to female ratio was 1:1.1. The frequency of JAK2 V617F positivity in our ET patients was found to be 61.9%. The mean hemoglobin was $11.7{\pm}2.4$ g/dl with a total leukocyte count of $13.3{\pm}8.1{\times}109/l$ and a platelet count of $1188{\pm}522{\times}109/l$. Positive correlations for JAK2 V617F mutation were established with high TLC count and raised LDH (P<0.05). No correlation of JAK2 V617F could be established with age and gender (P>0.05). Conclusions: JAK2 V617F mutation frequency in our ET patients was similar to those reported previously. Screening for the mutation in all suspected essential thrombocythemia cases could be beneficial in differentiating patients with reactive and clonal thrombocytosis.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1531-1533
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• 2016

Background: Polycythaemia rubra vera (PV) is a Philadelphia chromosome negative myeloproliferative neoplasm characterized by increased red cell production, independent of the mechanisms that regulate normal erythropoiesis. The aim of this study was to analyze the clinico-epidemiological profile of Pakistani patients with PV. Materials and Methods: In this retrospective cross sectional study, 26 patients with PV were enrolled from January 2010 to December 2014. They were diagnosed based on WHO criteria. Results: The mean age was $53.4{\pm}9.31years$ (range 36-72) and the male to female ratio was 2:1. Overall 30.7% of patients were asymptomatic. In symptomatic patients, major complaints were headache (30.8%), abdominal discomfort (23.1%), blurred vision (15.3%), pruritus (11.5%) and vascular incidents (11.5%). Physical examination revealed plethoric face and splenomegaly as predominant findings, detected in 34.6% and 30.7%, respectively, with the mean splenic span of $15.9{\pm}2.04cm$. The mean hemoglobin was $18.1{\pm}1.9g/dl$ with the mean hematocrit of $55.6{\pm}8.3%$. The mean total leukocyte count was $12.8{\pm}7.1{\times}10^9/l$ and the platelet count $511{\pm}341.9{\times}10^9/l$. Mean erythrocyte sedimentation rate was $3.5{\pm}1.22mm/hr$. Serum lactate dehydrogenase, serum creatinine and uric acid were $552.7{\pm}309.2$, $0.8{\pm}0.17$ and $6.60{\pm}1.89$ respectively. Conclusions: PV in Pakistani patients, unlike in the West, is seen in a moderately young population. The disease is frequently seen in male gender and primarily patients present with symptoms related to hyperviscosity.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7659-7661
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• 2015

Background: Essential thrombocythemia (ET) is a Philadelphia chromosome-negative myeloproliferative neoplasm characterized by sustained thrombocytosis and megakaryocytic hyperplasia. It is an uncommon hematological malignancy which primarily affects elderly individuals. The rational of this study was to determine its clinico-hematological profile along with risk stratification in Pakistan patients. Materials and Methods: In this retrospective cross sectional study, 21 patients with ET were enrolled from January 2011 to December 2014. Data was analyzed with SPSS version 21. Results: The mean age was $56.7{\pm}19.0years$ (range 18-87) and the male to female ratio was 1:1.1. Of the total, 62% of patients were above 50 years of age. Overall 61.9% were diagnosed incidentally and were asymptomatic. In symptomatic patients, major complaints were weakness (19%); erythromelalgia (14.2%), transit ischemic attack (9.5%) and gastrointestinal bleed (4.7%). The mean hemoglobin count was $11.7{\pm}2.4g/dl$ with a total leukocyte count of $13.3{\pm}8.1{\times}10^9/l$ and platelets count of $1188.8{\pm}522.2{\times}10^9/l$. Serum lactate dehydrogenase, serum creatinine and uric acid were $454.3{\pm}127.8$, $1.2{\pm}0.5$ and $7.4{\pm}3.4$ respectively. According to risk stratification, 57.1% were in high risk; 23.8% in intermediate risk while 19.1% in low risk group. Conclusions: ET in our patients in Pakistan, unlike in the West, is seen in a relatively young population. Primarily patients were asymptomatic and risk stratification revealed predominance of high risk disease in our setting.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7889-7892
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• 2015

Background: Primary idiopathic myelofibrosis (PMF) is a clonal Ph-chromosome negative myeloproliferative neoplasm characterized by dysregulated kinase signaling and release of abnormal cytokines. In the recent past, following JAK2 V617F mutation invention, important revolution has been made in the molecular diagnostic biology of this disease. The rational of this study was to determine the mutational status of JAK2 V617F in Pakistan patients with PMF. Materials and Methods: In this cross sectional study, 20 patients with PMF were enrolled from January 2011 to December 2014. Diagnosis was based on WHO criteria for PMF. All patients were screened for G-T point mutation (V617F) in the JAK2 gene on chromosome 9 by allele specific PCR. Results: The mean age was $57.9{\pm}16.5years$. The male to female ratio was 3:1. The frequency of JAK2 V617F positivity in our PMF patients was found to be 55%. Positive correlations of JAK2 V617F mutation were established with high TLC count, raised LDH and marked splenomegaly (P<0.05). No correlation of JAK2 V617F could be established with age and gender (P>0.05). Conclusions: The JAK2 V617F mutation frequency in our PMF patients was similar to those reported previously. In our hands JAK2 V617F mutated patients expressed an aggressive disease phenotype. Screening for the mutation in all suspected PMF cases could be beneficial in differentiating patients with reactive and clonal marrow fibrosis.

• The Journal of Internal Korean Medicine
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• v.42 no.5
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• pp.976-981
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• 2021

Objectives: This study investigated the effectiveness of acupuncture for improving polycythemia-vera-related symptoms and quality of life. Methods: A 56-year-old woman diagnosed with polycythemia vera received acupuncture treatment between February 19, 2021, and August 26, 2021. We observed the changes in subjective symptoms and conducted myeloproliferative neoplasm symptom assessment form total symptom score (MPN-SAF TSS) questionnaire. Results: After 13 acupuncture treatment sessions over six months, symptoms of polycythemia vera, such as fatigue, bone pain, itching, and headache, improved. Conclusion: This study suggests that acupuncture may be a helpful treatment strategy for polycythemia vera patients suffering from significant symptom burdens and reduced quality of life.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1019-1022
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• 2016

Background: Diagnostic difficulties in hematological malignancies may lead to unacceptably prolonged help-seeking to diagnostic interval as well as increased complications and poor outcomes. Proactive consultation by a clinical pathologist (PCCP) may help clinical diagnosis and therapeutic strategy. Hence, the aim of this investigation was to evaluate the effect of PCCP on the help-seeking to diagnostic interval in hematological cancer cases. Materials and Methods: From January to November, 2015, abnormal results of hematological laboratory testing with added laboratory comment were selectively screened out, and patients with such abnormalities in hematological laboratory testing and accompanied laboratory comment with PCCP were enrolled. Results: A total of 125 aberrant results of hematological laboratory testing were given with accompanied laboratory comments with PCCP and 40.8% (n=51) of these patient-oriented comments had an effect on clinical diagnosis and therapeutic strategy. Twelve of the subjects belonged to newly diagnosed hematological malignancies with the assistance of PCCP, and the help-seeking to diagnostic interval was also shortened from 42 days to 26 days in chronic lymphoid leukemia (CLL), from 83 days to 11 days in multiple myeloma (MM), and from 128 days to 15 days in myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN). During the monitoring interval, neither complication events nor deaths were reported in the study group. Conclusions: It was seemingly that PCCP prevented diagnostic delay in hematological malignancies via shortening the help-seeking to diagnostic interval, particularly in CLL, MM and MDS/MPN cases. PCCP can be considered to play an essential role in prompt establishment of diagnosis in hematological malignancies for those who newly present.