• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1681-1684
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• 2014

Objective: To investigate interferon (IFN) alpha 2 b for treating patients with JAK2V617F positive polycythemia vera (PV) and essential thrombocytosis (ET). Methods: Interferon alpha 2 b was used to treat patients with JAK2V617F positive PV and ET. In control group, hydroxyurea was used. Endpoint of study was to compare rates of hematological and molecular remission. Results: Patients in the interferon alpha 2 b group achieved higher rates of hematologic and molecular remission than patients in the hydroxyurea group, with a lower incidence of thrombosis. Conclusion: Compared with hydroxyurea, interferon alpha 2 b could reduce JAK2V617F load for patients with PV and ET, and achieve higher molecular remission, improve treatment efficacy and reduce complications.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3541-3546
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• 2014

TEL-AML1 fusion oncogene (t 12; 21) is the most common chromosomal abnormality in childhood acute lymphoblastic leukemia (ALL). This translocation is associated with a good prognosis and rarely shows chemotherapeutic resistance to 3-drug based remission induction phase of treatment as well as overall treatment. Thus, the higher the frequency of this fusion oncogene, the easier to manage childhood ALL in a given region with less intensive chemotherapy. Although global frequency of TEL-AML1 has been reported to be 20-30%, a very low frequency has been found in some geographical regions, including one study from Lahore, Punjab, Pakistan and others from India. The objective of present study was to investigate if this low frequency of TEL-AML1 in pediatric ALL is only in Lahore region or similar situation exists at other representative oncology centers of Pakistan. A total of 167 pediatric ALL patients were recruited from major pediatric oncology centers situated in Lahore, Faisalabad, Peshawar and Islamabad. Patients were tested for TEL-AML1 using nested reverse transcription polymerase chain reaction (RT-PCR). Only 17 out of 167 (10.2%) patients were found to be TEL-AML1 positive. TEL-AML1+ALL patients had favorable prognosis, most of them (82.4%, 14/17) showing early remission and good overall survival. Thus, our findings indicate an overall low frequency of TEL-AML1 in Pakistan pediatric ALL patients, in accordance with lower representation of this prognostically important genetic abnormality in other less developed countries, specifically in south Asia, thus associating it with poor living standards in these ethnic groups. It also indicates ethnic and geographical differences in the distribution of this prognostically important genetic abnormality among childhood ALL patients, which may have a significant bearing on ALL management strategies in different parts of the world.

• Clinical and Experimental Pediatrics
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• v.54 no.3
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• pp.95-105
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• 2011

Since the successful introduction of all-trans-retinoic acid (ATRA) and its combination with anthracycline-containing chemotherapy, the prognosis for acute promyelocytic leukemia (APL) has markedly improved. With ATRA and anthracycline-based-chemotherapy, the complete remission rate is greater than 90%, and the long-term survival rate is 70-89%. Moreover, arsenic trioxide (ATO), which was introduced for APL treatment in 1994, resulted in excellent remission rates in relapsed patients with APL, and more recently, several clinical studies have been designed to explore its role in initial therapy either alone or in combination with ATRA. APL is a rare disease in children and is frequently associated with hyperleukocytosis, which is a marker for higher risk of relapse and an increased incidence of microgranular morphology. The frequency of occurrence of the promyelocytic leu-kemia/retinoic acid receptor-alpha (PML/$RAR{\alpha}$) isoforms bcr 2 and bcr 3 is higher in children than in adults. Although recent clinical studies have reported comparable long-term survival rates in patients with APL, therapy for APL in children is challenging because of the risk of early death and the potential long-term cardiac toxicity resulting from the need to use high doses of anthracyclines. Additional prospective, randomized, large clinical trials are needed to address several issues in pediatric APL and to possibly minimize or eliminate the need for chemotherapy by combining ATRA and ATO. In this review article, we discuss the molecular pathogenesis, diagnostic progress, and most recent therapeutic advances in the treatment of children with APL.

• BMB Reports
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• v.48 no.8
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• pp.427-428
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• 2015

Despite high interests on microenvironmental regulation of leukemic cells, little is known for bone marrow (BM) niche in leukemia patients. Our recent study on BMs of acute myeloid leukemia (AML) patients showed that the mesenchymal stromal cells (MSCs) are altered during leukemic conditions in a clinical course-dependent manner. Leukemic blasts caused reprogramming of transcriptomes in MSCs and remodeling of niche cross-talk, selectively suppressing normal primitive hematopoietic cells while supporting leukemogenesis and chemo-resistance. Notably, differences in BM stromal remodeling were correlated to heterogeneity in subsequent clinical courses of AML, i.e., low numbers of mesenchymal progenitors at initial diagnosis were correlated to complete remission for 5-8 years, and high contents of mesenchymal progenitor or MSCs correlated to early or late relapse, respectively. Thus, stromal remodeling by leukemic cell is an intrinsic part of leukemogenesis that can contribute to the clonal dominance of leukemic cells over normal hematopoietic cells, and can serve as a biomarker for prediction of prognosis. [BMB Reports 2015; 48(8): 427-428]

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3025-3033
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• 2016

Chronic myeloid leukaemia (CML) is a clonal myeloproliferative hematopoietic stem cell disorder. Deregulated BCR-ABL fusion tyrosine kinase activity is the main cause of CML disease pathogenesis, making BCR-ABL an ideal target for inhibition. Current tyrosine kinase inhibitors (TKIs) designed to inhibit BCR-ABL oncoprotein activity, have completely transformed the prognosis of CML. Interruption of TKI treatment leads to minimal residual disease reside (MRD), thought to reside in TKI-insensitive leukaemia stem cells which remain a potential reservoir for disease relapse. This highlights the need to develop new therapeutic strategies for CML either as small molecule master TKIs or phytopharmaceuticals derived from nature to achieve chronic molecular remission. This review outlines the past, present and future therapeutic approaches for CML including coverage of relevant mechanisms, whether ABL dependent or independent, and epigenetic factors responsible for developing resistance against TKIs. Appearance of mutant clones along the course of therapy either pre-existing or induced due to therapy is still a challenge for the clinician. A proposed in-vitro model of generating colony forming units from CML stem cells derived from diagnostic samples seems to be achievable in the era of high throughput technology which can take care of single cell genomic profiling.

• The Journal of the Korean life insurance medical association
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• v.27 no.2
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• pp.68-74
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• 2008

Medical verification of cancer diagnosis in insurance claims is a very important procedure in insurance administrations. Claims staffs are in need of medical experts' opinions about claim administration. This procedure is called medical claim review (MCR) and is composed of verification and advice. MCR verification evaluates the insured’s physical condition by medical records and compares it with product coverage. It is divided into assessment of living assurance benefit, verification of cancer, and assessment of the cause of death. Actually cancer verification of MCR is applicable to coding because the risk ratio in product development is usually coded data. There are some confusing neoplastic diseases in assessing the verification of cancer. This article reviews gastrointestinal stromal tumors (GIST) and mucosa-associated lymphoid tissue tumors (MALToma) of the stomach. The second most common group of stromal or mesenchymal neoplasms affecting the gastrointestinal tract is GIST. Nowadays there are many articles about the pathophysiology of GIST. However there are few confirmative theories except molecular cell biology of KIT mutation and some tyrosine kinase. Therefore, coding the GIST, which has previously been classified as an intermediate risk group according to NIH2001 criteria, for cancer verification of MCR is suitable for D37.1; neoplasm of uncertain or unknown behavior of digestive organs and the stomach. The gastrointestinal tract is the predominant site of extranodal non-Hodgkin's lymphomas. B-cell lymphomas of the MALT type, now called extranodal marginal zone B-cell lymphoma of MALT type in the REAL/WHO classification, are the most common primary gastric lymphomas worldwide. Its characteristics are as follows. First, it is different from traditional stomach cancers such as gastric adenocarcinoma. Second, the primary therapy of MALToma is the eradication of H. pylori by antibiotics and the remission rate is over 80%. Third, it has a different clinical course compared to traditional malignant lymphoma. Someone insisted that cancer verification is not possible for the above reasons. However, there have been findings on pathologic mechanism, and according to WHO classification, MALToma is classified into malignant B-cell lymphoma and it must be verified as malignancy in MCR.

• Molecules and Cells
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• v.46 no.10
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• pp.611-626
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• 2023

Acute myeloid leukemia (AML) is a heterogeneous disease caused by distinctive mutations in individual patients; therefore, each patient may display different cell-type compositions. Although most patients with AML achieve complete remission (CR) through intensive chemotherapy, the likelihood of relapse remains high. Several studies have attempted to characterize the genetic and cellular heterogeneity of AML; however, our understanding of the cellular heterogeneity of AML remains limited. In this study, we performed single-cell RNA sequencing (scRNAseq) of bone marrow-derived mononuclear cells obtained from same patients at different AML stages (diagnosis, CR, and relapse). We found that hematopoietic stem cells (HSCs) at diagnosis were abnormal compared to normal HSCs. By improving the detection of the DNMT3A R882 mutation with targeted scRNAseq, we identified that DNMT3A-mutant cells that mainly remained were granulocyte-monocyte progenitors (GMPs) or lymphoid-primed multipotential progenitors (LMPPs) from CR to relapse and that DNMT3A-mutant cells have gene signatures related to AML and leukemic cells. Copy number variation analysis at the single-cell level indicated that the cell type that possesses DNMT3A mutations is an important factor in AML relapse and that GMP and LMPP cells can affect relapse in patients with AML. This study advances our understanding of the role of DNMT3A in AML relapse and our approach can be applied to predict treatment outcomes.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.6
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• pp.535-542
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• 2009

Purpose: This study was performed to know whether [$^{18}F$]Fluorothymidine (FLT) positron emission tomography (PET) can be used to monitor early response to radiotherapy in comparison with [$^{18}F$]Fluorodeoxyglucose (FDG) PET, and to establish the optimal imaging time for prediction of therapy response. Materials and Methods: Two patients with nasopharyngeal cancer underwent serial FLT PET and FDG PET before and during radiotherapy. Three on-treatment FLT and FDG PET scans were performed on 1 week, 2 weeks and 3 weeks (at each time of 10 Gy, 20 Gy and 30 Gy delivered). The peak standardized uptake values ($SUV_{peak}$) of primary tumors were measured on FLT and FDG PET. Then, percent changes of $SUV_{peak}$ after therapy were calculated. Results: In two patients, baseline values of $SUV_{peak}$ on FDT PET were higher than those on FLT PET (FLT vs FDG; 3.7 vs 5.0, and 5.7 vs 15.0). In patient 1, FLT $SUV_{peak}$ showed 78%, 78% and 84% of decrease on 1 week, 2 and 3 weeks after treatment, whereas FDG $SUV_{peak}$ showed 18%, 52% and 66% of decrease, respectively. In patient 2, FLT $SUV_{peak}$ showed 75%, 75% and 68% of decrease, whereas FDG $SUV_{peak}$ showed 51%, 49% and 58% of decrease, respectively. Both patients reached to complete remission after radiotherapy. Conclusion: After radiotherapy, the decrease of FLT tumor uptake preceded the decrease of FDG tumor uptake in patients with nasopharyngeal cancer, and 1 week after therapy may be appropriate time for the assessment of early response. FLT PET might be more useful than FDG PET for monitoring early response to radiotherapy.