Pub Date : 2021-06-02DOI: 10.26420/annhematoloncol.2021.1355
P. M, A. A, Omore I, S. K
A case of triple positive antiphospholipid syndrome in the setting of invasive adenocarcinoma of the rectosigmoid colon in a male.
男性直肠乙状结肠浸润性腺癌伴三阳性抗磷脂综合征1例。
{"title":"Triple Positive Antiphospholipid Syndrome in a Patient with Rectosigmoid Colon Cancer- a Rare Occurrence","authors":"P. M, A. A, Omore I, S. K","doi":"10.26420/annhematoloncol.2021.1355","DOIUrl":"https://doi.org/10.26420/annhematoloncol.2021.1355","url":null,"abstract":"A case of triple positive antiphospholipid syndrome in the setting of invasive adenocarcinoma of the rectosigmoid colon in a male.","PeriodicalId":72219,"journal":{"name":"Annals of hematology & oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47423028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-06-02DOI: 10.26420/annhematoloncol.2021.1357
G. Missassi, Ikoma-Colturato Mrv, Bortolucci Cm, Conte Je, Simioni Aj, Souza Mp, Colturato Var
Multiple Myeloma (MM) is one of the most common hematologic malignancies, with a heterogeneous prognosis. Therefore, the recognition of biomarkers can be useful to understand the differences in patient outcomes. Minimal Residual Disease (MRD) has been considered a very important prognostic factor in MM. In parallel, the prognostic value of immunophenotypic markers expressed in MM Plasma Cells (PCs) has also been described. The aim of this study was to assess the impact of CD27, CD28, CD45, CD56, CD117 and β2-microglobulin expressions on the outcome of 154 MM patients undergoing Autologous Stem Cell Transplantation (ASCT). The relation of each marker studied with the Overall Survival (OS) and Progression-Free Survival (PFS) was assessed, alone and in association with pre-ASCT MRD. Scores of good (GPM) and poor Prognostic Markers (PPM) were established, according to their respective survival curves. The expressions of CD27 and CD45 were associated to longer OS (p=0.013 and p=0.00, respectively) and PFS (p=0.00) as well as the absence of CD28 (OS p=0.026; PFS p=0.001) and CD56 (OS p=0.004; PFS p=0.009), in patients with undetectable MRD. The number of GPM showed an inverse correlation with the level of MRD (p=0.04), while a higher number of PPM was observed in patients with higher levels of MRD (p=0.04), which were also significantly associated with OS and PFS. In conclusion, although pre-ASCT MRD is a powerful prognostic factor in MM, these biomarkers can provide additional prognostic information and be used in the follow-up of MM patients.
{"title":"Immunophenotypic Markers Associated with Minimal Residual Disease Status and Outcome in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation","authors":"G. Missassi, Ikoma-Colturato Mrv, Bortolucci Cm, Conte Je, Simioni Aj, Souza Mp, Colturato Var","doi":"10.26420/annhematoloncol.2021.1357","DOIUrl":"https://doi.org/10.26420/annhematoloncol.2021.1357","url":null,"abstract":"Multiple Myeloma (MM) is one of the most common hematologic malignancies, with a heterogeneous prognosis. Therefore, the recognition of biomarkers can be useful to understand the differences in patient outcomes. Minimal Residual Disease (MRD) has been considered a very important prognostic factor in MM. In parallel, the prognostic value of immunophenotypic markers expressed in MM Plasma Cells (PCs) has also been described. The aim of this study was to assess the impact of CD27, CD28, CD45, CD56, CD117 and β2-microglobulin expressions on the outcome of 154 MM patients undergoing Autologous Stem Cell Transplantation (ASCT). The relation of each marker studied with the Overall Survival (OS) and Progression-Free Survival (PFS) was assessed, alone and in association with pre-ASCT MRD. Scores of good (GPM) and poor Prognostic Markers (PPM) were established, according to their respective survival curves. The expressions of CD27 and CD45 were associated to longer OS (p=0.013 and p=0.00, respectively) and PFS (p=0.00) as well as the absence of CD28 (OS p=0.026; PFS p=0.001) and CD56 (OS p=0.004; PFS p=0.009), in patients with undetectable MRD. The number of GPM showed an inverse correlation with the level of MRD (p=0.04), while a higher number of PPM was observed in patients with higher levels of MRD (p=0.04), which were also significantly associated with OS and PFS. In conclusion, although pre-ASCT MRD is a powerful prognostic factor in MM, these biomarkers can provide additional prognostic information and be used in the follow-up of MM patients.","PeriodicalId":72219,"journal":{"name":"Annals of hematology & oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41430670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-20DOI: 10.26420/annhematoloncol.2021.1351
A. DiPaola, C. Tortora, M. Argenziano, C. DiLeva, F. Rossi
Iron is a trace element essential for several physiological cell functions and any alteration in its metabolism could be associated to the onset of several disorders. Cells normally avoid any dysregulation, activating fine molecular mechanisms to balance iron uptake, utilization, recycling, storage and export. The main “actors” in this event are hepcidin, ferroportin, ferritin and transferrin, both at cell and systemic level. Dysregulation in iron homeostasis is closely related to inflammation onset and perpetuation, osteoporosis and cancer progression. During inflammation, it has been observed a reduction in circulating iron as direct consequence of increase in ferritin levels, aimed to contain inflammatory processes and in many cases to restore the immune response. Iron overload directly promotes bone resorption and inhibits bone formation inducing osteoporosis. Moreover, iron cellular accumulation is responsible for ROS production with consequent DNA damage and neoplastic transformation of cells. In conclusion, even though many molecular mechanisms have to be clarified, targeting iron and also the mediators of its metabolism could be useful to manage a great variety of disorders, such inflammation, immune diseases, osteoporosis and cancer.
{"title":"Iron Metabolism: From Inflammation to Cancer","authors":"A. DiPaola, C. Tortora, M. Argenziano, C. DiLeva, F. Rossi","doi":"10.26420/annhematoloncol.2021.1351","DOIUrl":"https://doi.org/10.26420/annhematoloncol.2021.1351","url":null,"abstract":"Iron is a trace element essential for several physiological cell functions and any alteration in its metabolism could be associated to the onset of several disorders. Cells normally avoid any dysregulation, activating fine molecular mechanisms to balance iron uptake, utilization, recycling, storage and export. The main “actors” in this event are hepcidin, ferroportin, ferritin and transferrin, both at cell and systemic level. Dysregulation in iron homeostasis is closely related to inflammation onset and perpetuation, osteoporosis and cancer progression. During inflammation, it has been observed a reduction in circulating iron as direct consequence of increase in ferritin levels, aimed to contain inflammatory processes and in many cases to restore the immune response. Iron overload directly promotes bone resorption and inhibits bone formation inducing osteoporosis. Moreover, iron cellular accumulation is responsible for ROS production with consequent DNA damage and neoplastic transformation of cells. In conclusion, even though many molecular mechanisms have to be clarified, targeting iron and also the mediators of its metabolism could be useful to manage a great variety of disorders, such inflammation, immune diseases, osteoporosis and cancer.","PeriodicalId":72219,"journal":{"name":"Annals of hematology & oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44761698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-20DOI: 10.26420/annhematoloncol.2021.1349
D. Supari, C. Weyhern, M. Kremer, J. Meyer, U. Heindl, M. Karthaus, H. Pohlmann
The recent introduction of immune checkpoint inhibitor therapy with anti- PD-1 agents has shown encouraging responses in gastrointestinal oncology. However, it is also known to possibly result in uncontrolled T cell autoreactivity, leading to a broad range of immune related adverse events. We present a patient who developed sequential immune-related hematologic and hepatic complications following pembrolizumab therapy for metastatic colon cancer. In particular, we describe in detail the histopathologic and immunohistochemical findings in the liver and bone marrow, adding to the spectrum of morphological changes which may be observed in association with PD-1 inhibitor therapy. The report also highlights the occurrence of these adverse reactions even after discontinuation of immunotherapy, eventually resulting in the death of the patient.
{"title":"Fatal Immune Response Associated with Anti-PD1: Pathological Insight","authors":"D. Supari, C. Weyhern, M. Kremer, J. Meyer, U. Heindl, M. Karthaus, H. Pohlmann","doi":"10.26420/annhematoloncol.2021.1349","DOIUrl":"https://doi.org/10.26420/annhematoloncol.2021.1349","url":null,"abstract":"The recent introduction of immune checkpoint inhibitor therapy with anti- PD-1 agents has shown encouraging responses in gastrointestinal oncology. However, it is also known to possibly result in uncontrolled T cell autoreactivity, leading to a broad range of immune related adverse events. We present a patient who developed sequential immune-related hematologic and hepatic complications following pembrolizumab therapy for metastatic colon cancer. In particular, we describe in detail the histopathologic and immunohistochemical findings in the liver and bone marrow, adding to the spectrum of morphological changes which may be observed in association with PD-1 inhibitor therapy. The report also highlights the occurrence of these adverse reactions even after discontinuation of immunotherapy, eventually resulting in the death of the patient.","PeriodicalId":72219,"journal":{"name":"Annals of hematology & oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47663488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-20DOI: 10.26420/annhematoloncol.2021.1350
D. Rouabhia, R. Audet, P. Desmeules, C. Labbé
Multiple lines of Anaplastic Lymphoma Kinase (ALK) Tyrosine Kinase Inhibitors (TKIs) are recommended for the treatment of ALK-positive Non-Small Cell Lung Cancer (NSCLC). This article provides an unusual case report of a 33-year-old male patient with a 91-month Progression-Free Survival (PFS) on a first-generation TKI, crizotinib.
{"title":"Stage IV ALK-Positive Lung Adenocarcinoma: 7.5-Year Complete Remission with Crizotinib","authors":"D. Rouabhia, R. Audet, P. Desmeules, C. Labbé","doi":"10.26420/annhematoloncol.2021.1350","DOIUrl":"https://doi.org/10.26420/annhematoloncol.2021.1350","url":null,"abstract":"Multiple lines of Anaplastic Lymphoma Kinase (ALK) Tyrosine Kinase Inhibitors (TKIs) are recommended for the treatment of ALK-positive Non-Small Cell Lung Cancer (NSCLC). This article provides an unusual case report of a 33-year-old male patient with a 91-month Progression-Free Survival (PFS) on a first-generation TKI, crizotinib.","PeriodicalId":72219,"journal":{"name":"Annals of hematology & oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42727834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-18DOI: 10.26420/annhematoloncol.2021.1348
M. Shobha, Baniya Ss, G. Sumit, S. Sunil, N. Yadav, P. Joyson
Merkel Cell Carcinoma (MCC) is a cutaneous neuroendocrine cancer with a poor prognosis. It is characterized by a high rate of recurrence and metastases to regional as well as distant sites. Clinically, MCC often manifests as a single painless, hard nodule in the sun-exposed area. The diameter is often <2cm, but in few cases, it can be >2cm, with rapid growth and metastases to lymph nodes. MCC carcinoma is diagnosed in the advanced stage because of its resemblance with other skin cancers. Because of the aggressive nature of this cancer, the overall prognosis is found to be poor. In this case report, we report a 71-year-old gentle male who presented with a painless mass in the right axilla three years ago, was diagnosed with MCC of the skin and was treated with surgical removal of the mass together with radiation therapy. Two years later, the follow-up visit restaging PET CT scan was done and was found to have a new intense uptake in the soft tissue nodule adjacent to the proximal sigmoid colon. Biopsy confirmed the metastasis of MCC to the colon. We are reporting an uncommon location of MCC metastasis to the intestine for which he got treated with immunotherapy.
{"title":"A Case Report on Recurrent Merkel Cell Carcinoma with Metastasis to Colon Treated with Pembrolizumab","authors":"M. Shobha, Baniya Ss, G. Sumit, S. Sunil, N. Yadav, P. Joyson","doi":"10.26420/annhematoloncol.2021.1348","DOIUrl":"https://doi.org/10.26420/annhematoloncol.2021.1348","url":null,"abstract":"Merkel Cell Carcinoma (MCC) is a cutaneous neuroendocrine cancer with a poor prognosis. It is characterized by a high rate of recurrence and metastases to regional as well as distant sites. Clinically, MCC often manifests as a single painless, hard nodule in the sun-exposed area. The diameter is often <2cm, but in few cases, it can be >2cm, with rapid growth and metastases to lymph nodes. MCC carcinoma is diagnosed in the advanced stage because of its resemblance with other skin cancers. Because of the aggressive nature of this cancer, the overall prognosis is found to be poor. In this case report, we report a 71-year-old gentle male who presented with a painless mass in the right axilla three years ago, was diagnosed with MCC of the skin and was treated with surgical removal of the mass together with radiation therapy. Two years later, the follow-up visit restaging PET CT scan was done and was found to have a new intense uptake in the soft tissue nodule adjacent to the proximal sigmoid colon. Biopsy confirmed the metastasis of MCC to the colon. We are reporting an uncommon location of MCC metastasis to the intestine for which he got treated with immunotherapy.","PeriodicalId":72219,"journal":{"name":"Annals of hematology & oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46150116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-10DOI: 10.26420/annhematoloncol.2021.1346
J. Jerez, M. Ocqueteau
Pure Red Cell Aplasia (PRCA) is an infrequent disease [1,2], which usually presents as hypogenerative normochromic anemia, and is characterized by a significant decrease (including absence) of erythroid precursors [3]. Its etiology can be congenital or acquired, and its correct diagnosis requires exclusion of alternative cases of refractory anemia, so the bone marrow histology plays a crucial role. Myelodisplastic Syndromes (MDS) should always be considered in its differential diagnosis. The use of laboratory tools, specifically Flow Cytometry (FCM) is gained importance in the study of malignant and benign hematology pathologies. In MDS, FCM is not yet considered a standard of care, however it provides valuable information [4,5] and there are numerous publications and scores for its usual clinical use (for example Ogata score and RED-score [6,7]). In relation to the rise of FCM in MDS, enormous progress has been made in the description of the erythroid precursors immunophenotype [8-10]. An example of normal erythroid maturation is presented in Figure 1, showing proerythroblasts with immunophenotype CD71+ CD105+ CD117+, basophilic erythroblasts CD71+ CD105+ CD117-, polychromatophilic and orthochromatophilic erythroblasts CD71+ CD105- CD117- distinguishing by size in Forward Scatter (FSC) versus CD36 respectively. Characteristic maturation curve in CD117 versus CD105 analysis evidenced a predominance towards more mature erythroblasts.
{"title":"Immunophenotype of Erythroid Precursors in Patient with Pure Red Cell Aplasia (PRCA): Utility of Analysis of Erythroid Maturation","authors":"J. Jerez, M. Ocqueteau","doi":"10.26420/annhematoloncol.2021.1346","DOIUrl":"https://doi.org/10.26420/annhematoloncol.2021.1346","url":null,"abstract":"Pure Red Cell Aplasia (PRCA) is an infrequent disease [1,2], which usually presents as hypogenerative normochromic anemia, and is characterized by a significant decrease (including absence) of erythroid precursors [3]. Its etiology can be congenital or acquired, and its correct diagnosis requires exclusion of alternative cases of refractory anemia, so the bone marrow histology plays a crucial role. Myelodisplastic Syndromes (MDS) should always be considered in its differential diagnosis. The use of laboratory tools, specifically Flow Cytometry (FCM) is gained importance in the study of malignant and benign hematology pathologies. In MDS, FCM is not yet considered a standard of care, however it provides valuable information [4,5] and there are numerous publications and scores for its usual clinical use (for example Ogata score and RED-score [6,7]). In relation to the rise of FCM in MDS, enormous progress has been made in the description of the erythroid precursors immunophenotype [8-10]. An example of normal erythroid maturation is presented in Figure 1, showing proerythroblasts with immunophenotype CD71+ CD105+ CD117+, basophilic erythroblasts CD71+ CD105+ CD117-, polychromatophilic and orthochromatophilic erythroblasts CD71+ CD105- CD117- distinguishing by size in Forward Scatter (FSC) versus CD36 respectively. Characteristic maturation curve in CD117 versus CD105 analysis evidenced a predominance towards more mature erythroblasts.","PeriodicalId":72219,"journal":{"name":"Annals of hematology & oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45901202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-04-16DOI: 10.26420/ANNHEMATOLONCOL.2021.1343
Martínez-Toldos Mc, R. Rodriguez, A. Marinsaldi, Rodriguez Gr, H. Guglielmone, M. E. Bernardi, A. Valdomero, G. Cuadra
The risk of thromboembolism with FIX replacement therapy remains a concern for hemophilic B patients. Previous studies from our laboratory demonstrated that the activated factor content of the FIX Plasma Derived (FIXpd) manufactured at UNC-Hemoderivados was negligible by in vitro assay. Despite this, we considered it important to conduct studies to assess the potential thrombogenic risk of our FIXpd concentrates using a modified stasis animal model. FIXpd were inject doses of 100 or 200 IU F IX kg-1 and some samples were supplemented with heparin (<0.5 of heparin/ IU FIX). Eight rats were tested at each dose level in the presence or absence of heparin, considering those samples with a thrombogenicity ≥2.0 as of potential thrombogenic risk. The mean scores ± SD 100 and 200 IU kg-1 in the presence or absence of heparin were 0.25±0.06 and 2.25±0.45 and 1.19±0.26 and 2.81±0.40, respectively. At both doses tested of FIXpd in the absence of heparin, there was no significant difference in mean scores (P<0.05). The encouraging data obtained from these animal experiments and results from in vitro tests, support the low thrombotic risk associated with the FIXpd concentrate manufactured in UNC Hemoderivados.
FIX替代疗法的血栓栓塞风险仍然是血友病B患者关注的问题。我们实验室之前的研究表明，通过体外检测，unc - hemderivatives公司生产的FIX血浆衍生(FIXpd)的活化因子含量可以忽略不计。尽管如此，我们认为有必要利用改良的停滞动物模型进行研究，评估FIXpd浓缩物的潜在血栓形成风险。FIXpd注射剂量为100或200 IU FIX kg-1，部分样品添加肝素(<0.5肝素/ IU FIX)。8只大鼠在肝素存在或不存在的情况下，在每个剂量水平下进行测试，考虑到这些样品的血栓形成性≥2.0作为潜在的血栓形成风险。肝素存在或不存在时的平均评分±SD 100和200 IU kg-1分别为0.25±0.06和2.25±0.45和1.19±0.26和2.81±0.40。在没有肝素的情况下，两种剂量的FIXpd测试，平均评分无显著差异(P<0.05)。从这些动物实验中获得的令人鼓舞的数据和体外试验的结果，支持与UNC血液衍生物制造的FIXpd浓缩物相关的低血栓形成风险。
{"title":"Assessment of Potential Thrombogenicity in an Animal Model of a Triple Viral Inactivated Factor IX Concentrate Manufactured in Argentina","authors":"Martínez-Toldos Mc, R. Rodriguez, A. Marinsaldi, Rodriguez Gr, H. Guglielmone, M. E. Bernardi, A. Valdomero, G. Cuadra","doi":"10.26420/ANNHEMATOLONCOL.2021.1343","DOIUrl":"https://doi.org/10.26420/ANNHEMATOLONCOL.2021.1343","url":null,"abstract":"The risk of thromboembolism with FIX replacement therapy remains a concern for hemophilic B patients. Previous studies from our laboratory demonstrated that the activated factor content of the FIX Plasma Derived (FIXpd) manufactured at UNC-Hemoderivados was negligible by in vitro assay. Despite this, we considered it important to conduct studies to assess the potential thrombogenic risk of our FIXpd concentrates using a modified stasis animal model. FIXpd were inject doses of 100 or 200 IU F IX kg-1 and some samples were supplemented with heparin (<0.5 of heparin/ IU FIX). Eight rats were tested at each dose level in the presence or absence of heparin, considering those samples with a thrombogenicity ≥2.0 as of potential thrombogenic risk. The mean scores ± SD 100 and 200 IU kg-1 in the presence or absence of heparin were 0.25±0.06 and 2.25±0.45 and 1.19±0.26 and 2.81±0.40, respectively. At both doses tested of FIXpd in the absence of heparin, there was no significant difference in mean scores (P<0.05). The encouraging data obtained from these animal experiments and results from in vitro tests, support the low thrombotic risk associated with the FIXpd concentrate manufactured in UNC Hemoderivados.","PeriodicalId":72219,"journal":{"name":"Annals of hematology & oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47794310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-04-16DOI: 10.26420/ANNHEMATOLONCOL.2021.1344
A. Kristl, K. Čamernik, S. Avbelj, M. Legiša
Enhanced glycolytic flux is a hallmarks of cancer cells. Posttranslational modification of the key regulatory enzyme of glycolysis, 6-Phosphofructo-1- Kinase (Pfk1) might trigger metabolic flux deregulation. In the cancer cells the human 85 kDa muscle type nPfk-M enzyme can be proteolytically cleaved to form highly-active 47 kDa shorter fragments that retain activity but become resistant to feed-back inhibition. In several tumorigenic cell lines, no native 85 kDa liver type nPfk-L isoforms could be either found and only 70 kDa shorter fragments were detected by immune-blotting. To learn more about the cancer-specific modified sfPfk-L enzyme, the truncated human sfPfk-L gene encoding 70 kDa fragments was inserted into the pfk null yeast S.cerevisiae cell. The recombinant modified enzyme showed higher affinity toward the substrate fructose-6-phosphate, reduced sensitivity toward the citrate and ATP inhibition in respect to the recombinant native PFK-L enzyme. Partially purified cancer-specific sfPfk-L fragments lacking the C-portion of the enzyme showed some instability under the diluted conditions in the buffer in respect to the tetrameric native nPfk-L enzyme. Growth characteristics of the yeast transformant encoding short sfPfk-L enzymes were similar to those encoding shorter sfPfk-M enzymes. No growth of the transformant with the sfPfk-L gene was observed on glucose but it grew faster than the transformant with the native human nPfk-L enzyme in a narrow ecological niche with low maltose concentration and 10 mM of ethanol in the medium. Similar to modified 47 kDa sfPfk-M fragments, also the short 70 kDa nPfk- Lfragments might cause deregulation of the glycolytic flux in the yeast and in the cancer cells. In yeast, deregulated metabolic flux unbalances redox potential that results in reduced growth rate. However, the cancer cells beat the redox unbalance by rapid re-oxidation of redundant NADH that results in lactate formation while the growth rate remains high.
{"title":"Another Form of Modified, Highly-Active 6-Phosphofructo-1-Kinase in Cancer Cells","authors":"A. Kristl, K. Čamernik, S. Avbelj, M. Legiša","doi":"10.26420/ANNHEMATOLONCOL.2021.1344","DOIUrl":"https://doi.org/10.26420/ANNHEMATOLONCOL.2021.1344","url":null,"abstract":"Enhanced glycolytic flux is a hallmarks of cancer cells. Posttranslational modification of the key regulatory enzyme of glycolysis, 6-Phosphofructo-1- Kinase (Pfk1) might trigger metabolic flux deregulation. In the cancer cells the human 85 kDa muscle type nPfk-M enzyme can be proteolytically cleaved to form highly-active 47 kDa shorter fragments that retain activity but become resistant to feed-back inhibition. In several tumorigenic cell lines, no native 85 kDa liver type nPfk-L isoforms could be either found and only 70 kDa shorter fragments were detected by immune-blotting. To learn more about the cancer-specific modified sfPfk-L enzyme, the truncated human sfPfk-L gene encoding 70 kDa fragments was inserted into the pfk null yeast S.cerevisiae cell. The recombinant modified enzyme showed higher affinity toward the substrate fructose-6-phosphate, reduced sensitivity toward the citrate and ATP inhibition in respect to the recombinant native PFK-L enzyme. Partially purified cancer-specific sfPfk-L fragments lacking the C-portion of the enzyme showed some instability under the diluted conditions in the buffer in respect to the tetrameric native nPfk-L enzyme. Growth characteristics of the yeast transformant encoding short sfPfk-L enzymes were similar to those encoding shorter sfPfk-M enzymes. No growth of the transformant with the sfPfk-L gene was observed on glucose but it grew faster than the transformant with the native human nPfk-L enzyme in a narrow ecological niche with low maltose concentration and 10 mM of ethanol in the medium. Similar to modified 47 kDa sfPfk-M fragments, also the short 70 kDa nPfk- Lfragments might cause deregulation of the glycolytic flux in the yeast and in the cancer cells. In yeast, deregulated metabolic flux unbalances redox potential that results in reduced growth rate. However, the cancer cells beat the redox unbalance by rapid re-oxidation of redundant NADH that results in lactate formation while the growth rate remains high.","PeriodicalId":72219,"journal":{"name":"Annals of hematology & oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49325865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-04-16DOI: 10.26420/ANNHEMATOLONCOL.2021.1342
Sahithi A, A. R., Prakash A, Jain Sk, B. P, J. A
Background: In thalassemia patients erythrocyte turnover rate increases due to chronic hemolysis and ineffective erythropoiesis leading to increase in uric acid production. Hyperuricosuria is one of the marker of proximal tubular dysfunction. Splenectomy can increase the risk of hyperuricemia by increasing erythrocyte turnover rate in Transfusion Dependent Thalassemia (TDT). Deferasirox enhances uric acid excretion from renal tubules leading to low serum uric acid levels. Methods: An institution based cross-sectional study was conducted from November 2018-March 2020 which included 60 adult TDT patients (≥18 years) attending Adult Thalassemia Day Care Centre at tertiary care hospital. Serum uric acid (mg/dl), 24 hour urinary uric acid (mg/dl), serum ferritin (ng/ml) were done. Results: Hyperuricemia was present in 20%, hypouricemia in 3.33%. Hyperuricosuria was present in 80%. Mean SUA levels were higher in males than females which was statistically significant (5.77±1.66 vs 4.64±1.44, p=0.007). There was statistically significant positive correlation between serum uric acid and serum creatinine(p = 0.0036) and age (p=0.0129). Hyperuricemia was more in subjects with intact spleen but was not statistically significant(p=0.104). Hyperuricemia had negative association with deferasirox therapy [1 (3.03%) vs 11 (40.74%), p=0.0004] compared with normouricemia subjects. Conclusion: Uric acid abnormalities were seen in 23.3% of patients. Hyperuricemia was present in one fourth of the patients and significant risk factors were increasing age, male gender, rising serum creatinine. Deferasirox therapy was negatively associated with hyperuricemia. Tubular dysfunction is relatively common in TDT as more than three fourth patients had hyperuricosuria. Regular monitoring of serum uric acid and urinary uric acid is recommended.
背景:在地中海贫血患者中，由于慢性溶血和无效的红细胞生成导致尿酸生成增加，红细胞周转率增加。高尿量是近端肾小管功能障碍的标志之一。脾切除术可以增加输血依赖型地中海贫血(TDT)的红细胞周转率，从而增加高尿酸血症的风险。去铁铁增强尿酸从肾小管排泄导致低血清尿酸水平。方法:2018年11月至2020年3月进行了一项基于机构的横断面研究，纳入了在三级医院成人地中海贫血日托中心就诊的60名成人TDT患者(≥18岁)。测定血清尿酸(mg/dl)、24小时尿尿酸(mg/dl)、血清铁蛋白(ng/ml)。结果:高尿酸血症占20%，低尿酸血症占3.33%。80%出现高尿酸血症。男性平均SUA水平高于女性，差异有统计学意义(5.77±1.66 vs 4.64±1.44,p=0.007)。血清尿酸、肌酐与年龄(p=0.0129)呈正相关，差异有统计学意义(p= 0.0036)。脾脏完好者高尿酸血症发生率较高，但无统计学意义(p=0.104)。与正常尿毒症患者相比，高尿酸血症与去铁霉素治疗呈负相关[1 (3.03%)vs 11 (40.74%)， p=0.0004]。结论:23.3%的患者存在尿酸异常。四分之一的患者存在高尿酸血症，显著的危险因素是年龄增加、男性、血清肌酐升高。去铁铁治疗与高尿酸血症呈负相关。小管功能障碍在TDT中相对常见，超过四分之三的患者有高尿量。建议定期监测血清尿酸和尿尿酸。
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