Association between c-Myc Expression with Clinicopathological Features in T And NK Cell Lymphomas

Hasenan, Nasrun; Isa, Seoparjoo Azmel Mohd; Hussain, Faezahtul Arbaeyah

doi:10.31557/apjcp.2021.22.12.4011

Cited by 4 publications

(3 citation statements)

References 34 publications

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“…The T allele of rs10094872 is associated with PDAC risk; this variant is situated near the MYC proto-oncogene. MYC plays a role in cell cycle progression, apoptosis, and cellular transformation, and mutations in this gene are frequently observed in numerous human cancers (55)(56)(57)(58)(59)(60). Although these associations are intriguing, they are not statistically significant when applying multiple testing corrections.…”

Section: Genetic Background and Ipmn Progressionmentioning

confidence: 99%

Role of pancreatic ductal adenocarcinoma risk factors in intraductal papillary mucinous neoplasm progression

et al. 2023

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IntroductionPancreatic ductal adenocarcinoma (PDAC) is lethal due to its late diagnosis and lack of successful treatments. A possible strategy to reduce its death burden is prevention. Intraductal papillary mucinous neoplasms (IPMNs) are precursors of PDAC. It is difficult to estimate the incidence of IPMNs because they are asymptomatic. Two recent studies reported pancreatic cysts in 3% and 13% of scanned subjects. The possibility of identifying a subgroup of IPMN patients with a higher probability of progression into cancer could be instrumental in increasing the survival rate. In this study, genetic and non-genetic PDAC risk factors were tested in a group of IPMN patients under surveillance.MethodsA retrospective study was conducted on 354 IPMN patients enrolled in two Italian centres with an average follow-up of 64 months. With the use of DNA extracted from blood, collected at IPMN diagnosis, all patients were genotyped for 30 known PDAC risk loci. The polymorphisms were analysed individually and grouped in an unweighted polygenic score (PGS) in relation to IPMN progression. The ABO blood group and non-genetic PDAC risk factors were also analysed. IPMN progression was defined based on the development of worrisome features and/or high-risk stigmata during follow-up.ResultsTwo genetic variants (rs1517037 and rs10094872) showed suggestive associations with an increment of IPMN progression. After correction for multiple testing, using the Bonferroni correction, none of the variants showed a statistically significant association. However, associations were observed for the non-genetic variables, such as smoking status, comparing heavy smokers with light smokers (HR = 3.81, 95% 1.43–10.09, p = 0.007), and obesity (HR = 2.46, 95% CI 1.22–4.95, p = 0.012).ConclusionIn conclusion, this study is the first attempt to investigate the presence of shared genetic background between PDAC risk and IPMN progression; however, the results suggest that the 30 established PDAC susceptibility polymorphisms are not associated with clinical IPMN progression in a sample of 354 patients. However, we observed indications of cigarette smoking and body mass index (BMI) involvement in IPMN progression. The biological mechanism that could link these two risk factors to progression could be chronic inflammation, of which both smoking and obesity are strong promoters.

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Section: Genetic Background and Ipmn Progressionmentioning

confidence: 99%

Role of pancreatic ductal adenocarcinoma risk factors in intraductal papillary mucinous neoplasm progression

et al. 2023

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“…2. p53 [21] mutations in PTCL and 3. MYC expression [22] in NK/T-cell lymphoma make the disease refractory to treatment. In children with acute leukemia, FLT3 gene mutations affecting the expression of 4. equilibrative nucleoside transporter 1 (ENT-1) [23], which mediates uptake of cylocide into leukemia cells, make the disease refractory to treatment.…”

Section: Introduction (A Brief Review)mentioning

confidence: 99%

Possible New Histological Prognostic Index for Aggressive Mature T-cell Lymphoma (TCL Urayasu Classification)— a Brief Review of the Literature on the Functional Proteins Involved in Refractory Hematologic Malignancy—

Nitta,

Takizawa,

Mitsumori

et al. 2024

Preprint

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Aggressive mature T-cell lymphoma (TCL) is a disease that carries a poor prognosis. The mechanism, at the functional protein level, of the resistance to therapy of TCL has not yet been well clarified. To comprehensively clarify the mechanism, we first reviewed the literature, as mentioned in the Introduction section, on 22 types of representative functional proteins reported as being potentially associated with treatment resistance, mainly in hematologic tumors. Next, we retrospectively analyzed the tumor cell expressions of these 22 functional proteins in 16 randomly selected patients with TCL who had received CHOP (cyclophosphamide, hydroxyl doxorubicin, oncovin, and prednisolone) therapy as first-line treatment. As a result, we propose a new three-group prognostic classification of TCL (the TCL Urayasu Classification) based on the mechanism of resistance to treatment of these tumors. The study subjects included 7 patients (44%) with peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), 6 patients (38%) with angioimmunoblastic T-cell lymphoma (AITL), and 3 patients (19%) with anaplastic large T-cell lymphoma (ALCL). Immunohistochemistry was performed in paraffin-embedded tumor tissue sections prepared from these patients as antigens using antibodies against the 22 previously reported treatment-resistance-related proteins to determine the tumor cell expression statuses of these proteins. Log-rank test was performed to compare the overall survival (OS) after CHOP therapy of the patients showing positive and negative immunostaining for these proteins, as well as among patients grouped based on other factors. Overall, the median OS of the TCL patients was about 33.5 months. When compared by the disease type, the prognosis was found to be worse in the order of ALCL, AITL, and PTCL. A multivariate analysis showed that expression of glucose-regulated protein 94 (GRP94), a protein that serves as a pro-survival component under endoplasmic reticulum (ER) stress in the tumor microenvironment, was significantly associated with shortened survival. No significant difference was observed for the conventional poor prognostic factors: high-risk International Prognostic Index (IPI) and high-risk Prognostic Index for peripheral T-cell lymphoma, unspecified (PTCL-U) (PIT). However, when GRP94 was combined with six other factors, listed below, as survival-shortening factors, significant differences were observed. The 6 factors were 1) programmed cell death-ligand 1 (PD-L1) and 2) programmed cell death 1 (PD-1), which are involved in immune surveillance; 3) aldo-keto reductase family 1 member C3 (AKR1C3), which is an enzyme that inactivates HO (hydroxyl doxorubicin [H] and oncovin [O]) of CHOP; 4) P53, a tumor suppressor; 5) Glucose-regulated protein 78 (GRP78), an ER stress protein; 6) thymidine phosphorylase (TP), which is an enzyme involved in thymidine catabolism. Based on the combination of GRP94 and the six other factors expressed in the tumors, we propose a new prognostic classification system for TCL (TCL Urayasu classification). Group 1 (group with a relatively good prognosis): GRP94-negative (n = 6; median OS, 88 months; p < 0.01); Group 2 (group with a poor prognosis): GRP94-positive, plus expression of 2 of the 6 aforementioned factors (n = 5; median OS, 25 months; p > 0.05); and Group 3 (group with a very poor prognosis): GRP94-positive, plus expression of at least 3 of the 6 aforementioned factors (n = 5; median OS, 10 months; p < 0.01). Thus, the TCL Urayasu prognostic classification is a simple, useful, and innovative classification that also explains the mechanism of resistance to treatment for each functional protein. Accumulation of more cases and further analyses are expected in the future to enable clinical application, such as use of a stratified treatment approach and treatment using inhibitors.

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“…Ten (31.3%) were treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) as the first line treatment. Eleven (34.4%) patients died in the follow-up period, eight of whom had C-MYC expression 24.…”

mentioning

confidence: 99%

Non-Hodgkin lymphoma research (excluding all B cell lymphoma) in Malaysia: A review

Ghee Lim

2023

IeJSME

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Introduction: Lymphoma is a diverse group of malignant proliferations that arise as discrete tissue masses. The 5 th edition of the World Health Organization classification of Tumours of Haematopoietic and Lymphoid Tissues was released on 22 nd June 2022. The WHO-HAEM5 classification of Mature T and NK neoplasms is further subclassified into various categories which are detailed in this review. Methods: A search was conducted using bibliographic databases, various repositories, and the Clinical Research Centre website retrieving journal articles, conference proceedings, book Chapters, guidelines, and thesis. The search terms used were Malaysia AND lymphoma. Results:The search earmarked a total of 561 papers. There were nine case series retrieved from 1967 to 2022. The site, age distribution, prognostic markers, and the various subclassification of NK/T cell lymphomas were studied. The gastrointestinal tract was the commonest site for extranodal lymphomas. Prognostic markers associated were EBV, C-MYC protein and staining for CD2, CD3, CD20, CD56, and CD57 antigens.For anaplastic large cell lymphoma (ALCL), CD30 (Ki-1) and ALK antigens were noted as important. The use of 18F-Fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) has emerged as an important investigation. Various chemotherapeutic regimens, surgical interventions where necessary and autologous peripheral blood stem cell transplantation when indicated are the mainstay of treatment. Conclusion:Research on NK/T cell lymphoma, including ALCL, has been ongoing in recent years. This review adds on to the existing literature on lymphoma in Malaysia that can lead to further research, into the diagnosis and treatment of lymphoma in Malaysia and around the world.

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Association between c-Myc Expression with Clinicopathological Features in T And NK Cell Lymphomas

Cited by 4 publications

References 34 publications

Role of pancreatic ductal adenocarcinoma risk factors in intraductal papillary mucinous neoplasm progression

Role of pancreatic ductal adenocarcinoma risk factors in intraductal papillary mucinous neoplasm progression

Possible New Histological Prognostic Index for Aggressive Mature T-cell Lymphoma (TCL Urayasu Classification)— a Brief Review of the Literature on the Functional Proteins Involved in Refractory Hematologic Malignancy—

Non-Hodgkin lymphoma research (excluding all B cell lymphoma) in Malaysia: A review

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