F. Sharpley, Hannah Miller, R. Spencer, Dane Bradwell, Janet Parkinson, Yvette Ibbotson, S. Jowitt
In the UK, approximately 5820 new cases of multiple myeloma (MM) are diagnosed each year. This number has increased by a third since the early 1990s. Considerable progress has been achieved in our ability to treat MM as a result of the development of new chemotherapeutic agents. MM is a disease more commonly seen in elderly individuals who frequently have pre-existing co-morbidities and are subject to social pressures that impact adversely on their quality of life (QOL). As their lives are extended by more effective treatment of MM, there is a greater need to address such issues. This review will focus on the holistic needs of a patient with MM, and how all members of the multidisciplinary team have a role. The aim is to advocate for centres to support MM patients to live well with their condition.
{"title":"Is It Time for a More Holistic Approach to the Treatment of Multiple Myeloma?","authors":"F. Sharpley, Hannah Miller, R. Spencer, Dane Bradwell, Janet Parkinson, Yvette Ibbotson, S. Jowitt","doi":"10.3390/hemato2040040","DOIUrl":"https://doi.org/10.3390/hemato2040040","url":null,"abstract":"In the UK, approximately 5820 new cases of multiple myeloma (MM) are diagnosed each year. This number has increased by a third since the early 1990s. Considerable progress has been achieved in our ability to treat MM as a result of the development of new chemotherapeutic agents. MM is a disease more commonly seen in elderly individuals who frequently have pre-existing co-morbidities and are subject to social pressures that impact adversely on their quality of life (QOL). As their lives are extended by more effective treatment of MM, there is a greater need to address such issues. This review will focus on the holistic needs of a patient with MM, and how all members of the multidisciplinary team have a role. The aim is to advocate for centres to support MM patients to live well with their condition.","PeriodicalId":93705,"journal":{"name":"Hemato","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44875270","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}
F. Maccioni, Alessandro Calabrese, L. Manganaro, C. de Felice, Sara Cardaccio, M. López, Arianna Cleri, G. Capriotti, L. Petrucci, C. Catalano, A. Pulsoni
(1) Background: The purpose of this study is to retrospectively compare CT, MRI, and PET/CT in detecting lymphadenopathies and extra-nodal lesions in lymphoma and in disease staging. (2) Methods: Inclusion criteria were the availability of TB (Total Body) CT and/or PET/CT performed before treatment; MRI performed no later than 2 weeks after TBCT; histological confirmation of lymphoma; clinical-diagnostic follow-up. Using these criteria, we included 64/353 patients with TBCT and MRI performed at our hospital; 20/64 had PET/CT performed in other hospitals. Histology and follow-up were gold standard. (3) Results: The sensitivity, specificity, and accuracy in lymph nodes detection was 84.5%, 94.4%, and 91% for CT and 95%, 98.9%, and 95.6% for MRI. High agreement was observed between CT and MRI regarding the number and size of positive lymph nodes and for disease staging. MRI identified eight more extra-nodal lesions than CT. In the subgroup of 20 patients, PET/CT did not show a significant superiority in sensitivity, specificity, accuracy, and staging ability than CT and MRI. (4) Conclusions: Our study demonstrates a mild superiority of MRI over CT in lymphoma staging. Although PET/CT remains the reference standard, MRI demonstrated a similar diagnostic accuracy, with the added value of being radiation-free.
{"title":"MRI versus CT and PET/CT in the Preoperative Assessment of Hodgkin and Non-Hodgkin Lymphomas","authors":"F. Maccioni, Alessandro Calabrese, L. Manganaro, C. de Felice, Sara Cardaccio, M. López, Arianna Cleri, G. Capriotti, L. Petrucci, C. Catalano, A. Pulsoni","doi":"10.3390/hemato2040041","DOIUrl":"https://doi.org/10.3390/hemato2040041","url":null,"abstract":"(1) Background: The purpose of this study is to retrospectively compare CT, MRI, and PET/CT in detecting lymphadenopathies and extra-nodal lesions in lymphoma and in disease staging. (2) Methods: Inclusion criteria were the availability of TB (Total Body) CT and/or PET/CT performed before treatment; MRI performed no later than 2 weeks after TBCT; histological confirmation of lymphoma; clinical-diagnostic follow-up. Using these criteria, we included 64/353 patients with TBCT and MRI performed at our hospital; 20/64 had PET/CT performed in other hospitals. Histology and follow-up were gold standard. (3) Results: The sensitivity, specificity, and accuracy in lymph nodes detection was 84.5%, 94.4%, and 91% for CT and 95%, 98.9%, and 95.6% for MRI. High agreement was observed between CT and MRI regarding the number and size of positive lymph nodes and for disease staging. MRI identified eight more extra-nodal lesions than CT. In the subgroup of 20 patients, PET/CT did not show a significant superiority in sensitivity, specificity, accuracy, and staging ability than CT and MRI. (4) Conclusions: Our study demonstrates a mild superiority of MRI over CT in lymphoma staging. Although PET/CT remains the reference standard, MRI demonstrated a similar diagnostic accuracy, with the added value of being radiation-free.","PeriodicalId":93705,"journal":{"name":"Hemato","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42238033","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}
Immunoglobulin light chain (AL) amyloidosis is the most common type of systemic amyloidosis in China and is associated with increased morbidity and a poor prognosis. However, the clinical characteristics of Chinese patients with AL amyloidosis have not been systematically investigated. This scoping review aimed to summarize the available literature regarding the clinical characteristics of patients with AL amyloidosis and identify potential knowledge gaps. We searched three electronic databases from inception to 7 February 2021. PICOS (Patient, Intervention, Comparison, Outcome and Study) design structure was used to formulate the data extraction. All statistical calculations and analyses were performed with R (version 3.6.0). Sixty-seven articles with 5022 patients were included. Results suggest Chinese patients were younger (57 years) at the time of diagnosis when compared with other patient populations and were predominantly male (61.2%). The time interval from the onset of symptoms to diagnosis was between 6 and 12 months. It was found that 41.1% of Chinese patients with AL amyloidosis were diagnosed with an advanced stage III disease when diagnosed, and 20.2% had a concurrent disease. The most involved organs were the kidneys (84.3%) and the heart (62.5%). In conclusion, our study shows some similarities and differences with other studies on the clinical characteristics of Chinese patients with AL amyloidosis, including the age at diagnosis, Mayo stage, and organ involvement. However, a nationwide epidemiological investigation is still needed to provide a comprehensive overview of this patient population in China.
免疫球蛋白轻链(AL)淀粉样变是中国最常见的系统性淀粉样变类型，发病率增高，预后不良。然而，中国AL淀粉样变患者的临床特征尚未得到系统的研究。本综述旨在总结关于AL淀粉样变患者临床特征的现有文献，并找出潜在的知识空白。我们检索了从成立到2021年2月7日的三个电子数据库。采用PICOS (Patient, Intervention, Comparison, outcomes and Study)设计结构制定数据提取。所有统计计算和分析均使用R(版本为3.6.0)进行。纳入67篇文章，5022例患者。结果显示，与其他患者人群相比，中国患者在诊断时更年轻(57岁)，且以男性为主(61.2%)。从症状出现到诊断的时间间隔为6至12个月。结果发现，41.1%的中国AL淀粉样变患者在诊断时诊断为晚期III期疾病，20.2%的患者有并发疾病。受累最多的器官是肾脏(84.3%)和心脏(62.5%)。总之，我们的研究与其他研究在中国AL淀粉样变患者的临床特征，包括诊断年龄、Mayo分期和器官受累方面有一些相似之处，也有一些差异。然而，仍需要开展全国性的流行病学调查，以提供中国这一患者群体的全面概况。
{"title":"The clinical characteristics of immunoglobulin light chain amyloidosis in Chinese population: A systematic scoping review","authors":"Cheng-li Fu, Xiaohong Wang, X. Cao, Lingjie Xu, Wanggen Liu, Jingnan Pi, Bin Wang, Wenming Chen","doi":"10.37766/inplasy2021.9.0086","DOIUrl":"https://doi.org/10.37766/inplasy2021.9.0086","url":null,"abstract":"Immunoglobulin light chain (AL) amyloidosis is the most common type of systemic amyloidosis in China and is associated with increased morbidity and a poor prognosis. However, the clinical characteristics of Chinese patients with AL amyloidosis have not been systematically investigated. This scoping review aimed to summarize the available literature regarding the clinical characteristics of patients with AL amyloidosis and identify potential knowledge gaps. We searched three electronic databases from inception to 7 February 2021. PICOS (Patient, Intervention, Comparison, Outcome and Study) design structure was used to formulate the data extraction. All statistical calculations and analyses were performed with R (version 3.6.0). Sixty-seven articles with 5022 patients were included. Results suggest Chinese patients were younger (57 years) at the time of diagnosis when compared with other patient populations and were predominantly male (61.2%). The time interval from the onset of symptoms to diagnosis was between 6 and 12 months. It was found that 41.1% of Chinese patients with AL amyloidosis were diagnosed with an advanced stage III disease when diagnosed, and 20.2% had a concurrent disease. The most involved organs were the kidneys (84.3%) and the heart (62.5%). In conclusion, our study shows some similarities and differences with other studies on the clinical characteristics of Chinese patients with AL amyloidosis, including the age at diagnosis, Mayo stage, and organ involvement. However, a nationwide epidemiological investigation is still needed to provide a comprehensive overview of this patient population in China.","PeriodicalId":93705,"journal":{"name":"Hemato","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46947711","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}
Elise Aasebø, A. Brenner, M. Hernandez-Valladares, E. Birkeland, H. Reikvam, F. Selheim, F. Berven, Ø. Bruserud
In vitro culture is widely used for characterization of primary human acute myeloid leukemia (AML) cells, but even when using optimized handling and culture conditions the AML cells show spontaneous in vitro apoptosis with a gradual decrease in cell viability during culture. The extent of this stress-induced apoptosis varies between patients, and a high degree of apoptosis is associated with high pre-culture BCL2 levels together with low levels of BAX and Heat Shock Proteins 30 and 90. We compared the global proteomic profiles during ongoing in vitro apoptosis for patients with high and low AML cell viability (i.e., less extensive versus extensive spontaneous apoptosis) after 48 h of culture. We identified 7902 proteins, but only 276 proteins differed significantly between patients with high (i.e., >25% viable cells; 192 upregulated and 84 downregulated peptides) and low viability after in vitro culture. Protein interaction network analysis based on these 276 protein identified three protein networks that included 18 proteins; most of these proteins were localized to the endoplasmic reticulum and several of them are involved in or are altered during the process of endoplasmic reticulum stress/unfolded protein stress response. To conclude, primary AML cells are heterogeneous with regard to degree of apoptosis in response to cellular stress, and this difference in regulation of apoptosis is associated with differences in the induction of and/or response to the unfolded protein stress response.
{"title":"Proteomic Characterization of Spontaneous Stress-Induced In Vitro Apoptosis of Human Acute Myeloid Leukemia Cells; Focus on Patient Heterogeneity and Endoplasmic Reticulum Stress","authors":"Elise Aasebø, A. Brenner, M. Hernandez-Valladares, E. Birkeland, H. Reikvam, F. Selheim, F. Berven, Ø. Bruserud","doi":"10.3390/hemato2030039","DOIUrl":"https://doi.org/10.3390/hemato2030039","url":null,"abstract":"In vitro culture is widely used for characterization of primary human acute myeloid leukemia (AML) cells, but even when using optimized handling and culture conditions the AML cells show spontaneous in vitro apoptosis with a gradual decrease in cell viability during culture. The extent of this stress-induced apoptosis varies between patients, and a high degree of apoptosis is associated with high pre-culture BCL2 levels together with low levels of BAX and Heat Shock Proteins 30 and 90. We compared the global proteomic profiles during ongoing in vitro apoptosis for patients with high and low AML cell viability (i.e., less extensive versus extensive spontaneous apoptosis) after 48 h of culture. We identified 7902 proteins, but only 276 proteins differed significantly between patients with high (i.e., >25% viable cells; 192 upregulated and 84 downregulated peptides) and low viability after in vitro culture. Protein interaction network analysis based on these 276 protein identified three protein networks that included 18 proteins; most of these proteins were localized to the endoplasmic reticulum and several of them are involved in or are altered during the process of endoplasmic reticulum stress/unfolded protein stress response. To conclude, primary AML cells are heterogeneous with regard to degree of apoptosis in response to cellular stress, and this difference in regulation of apoptosis is associated with differences in the induction of and/or response to the unfolded protein stress response.","PeriodicalId":93705,"journal":{"name":"Hemato","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46791255","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}
Megumi Uemichi, Kota Yokoyama, J. Tsuchiya, Toshiki Terao, Y. Machida, K. Matsue, U. Tateishi
To clarify the prognostic value of 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in Neurolymphomatosis (NL), we retrospectively reviewed medical records of all NL patients who had undergone 18F-FDG PET/CT from 2007 to 2020 at Kameda Medical Center and Tokyo Medical and Dental University Hospital. The clinical data of patients were compared with 18F-FDG PET/CT findings of number of nerve lesions and presence of non-nerve extranodal lesions (ENL). Subsequently, we calculated recurrence-free survival (RFS) and overall survival (OS) using the Kaplan–Meier method. A total of 28 patients (mean age 70.1 years, range 44–87 years; 15 women) were included in the study and 7 patients (25.0%) relapsed NL. The number of nerve lesions detected by 18F-FDG PET/CT ranged from 1 to 5, with an average of 2.02. ENL was observed in 18 cases (64.3%). The comparison between the findings revealed that the more the lesions detected by 18F-FDG PET/CT, the higher the probability of recurrence (χ2 = 13.651, p = 0.0085) and there was significantly shorter RFS for the patients with 3 or more nerve lesions (p = 0.0059), whereas the presence of ENL was not significantly associated with any clinical findings. The present study revealed that the more nerve lesions detected by 18F-FDG PET/CT, the poorer the recurrence rate and RFS.
{"title":"Impact of 18F-FDG PET/CT in Predicting Recurrence in Neurolymphomatosis","authors":"Megumi Uemichi, Kota Yokoyama, J. Tsuchiya, Toshiki Terao, Y. Machida, K. Matsue, U. Tateishi","doi":"10.3390/hemato2030038","DOIUrl":"https://doi.org/10.3390/hemato2030038","url":null,"abstract":"To clarify the prognostic value of 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in Neurolymphomatosis (NL), we retrospectively reviewed medical records of all NL patients who had undergone 18F-FDG PET/CT from 2007 to 2020 at Kameda Medical Center and Tokyo Medical and Dental University Hospital. The clinical data of patients were compared with 18F-FDG PET/CT findings of number of nerve lesions and presence of non-nerve extranodal lesions (ENL). Subsequently, we calculated recurrence-free survival (RFS) and overall survival (OS) using the Kaplan–Meier method. A total of 28 patients (mean age 70.1 years, range 44–87 years; 15 women) were included in the study and 7 patients (25.0%) relapsed NL. The number of nerve lesions detected by 18F-FDG PET/CT ranged from 1 to 5, with an average of 2.02. ENL was observed in 18 cases (64.3%). The comparison between the findings revealed that the more the lesions detected by 18F-FDG PET/CT, the higher the probability of recurrence (χ2 = 13.651, p = 0.0085) and there was significantly shorter RFS for the patients with 3 or more nerve lesions (p = 0.0059), whereas the presence of ENL was not significantly associated with any clinical findings. The present study revealed that the more nerve lesions detected by 18F-FDG PET/CT, the poorer the recurrence rate and RFS.","PeriodicalId":93705,"journal":{"name":"Hemato","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48361494","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}
G. Restivo, L. Mussolin, P. D’Angelo, Angela Trizzino, S. Ialuna, E. Sabattini, Cristina Gallo, A. Toscano, E. Carraro, M. Pillon, P. Farruggia
Anaplastic large cell lymphoma (ALCL) is a histological subtype of non-Hodgkin lymphoma, largely characterized by anaplastic lymphoma kinase (ALK) positivity, resulting from the chromosomal translocation t(2;5). We report a pediatric case of ALK-positive ALCL with primary concomitant involvement of bone and central nervous system (CNS); thereafter, a literature review about pediatric primary bone and primary CNS ALCL was conducted. According to the analyzed data, our case is unique because it is characterized by the contemporary involvement of the spine and CNS. During and after chemotherapy, our patient was monitored by detecting minimal residual disease (MRD) through the analysis of fusion transcript nucleophosmin-ALK. MRD assessment, not only in bone marrow but also in peripheral blood, seems to be a very powerful tool for predicting the prognosis of pediatric ALCL patients, as already described in the literature. Moreover, as shown in our case, it could be used during the follow-up for early recognition of relapse.
{"title":"Pediatric Anaplastic Large Cell Lymphoma with Concomitant Involvement of Spine and Central Nervous System: A Case Report and Review of Literature","authors":"G. Restivo, L. Mussolin, P. D’Angelo, Angela Trizzino, S. Ialuna, E. Sabattini, Cristina Gallo, A. Toscano, E. Carraro, M. Pillon, P. Farruggia","doi":"10.3390/hemato2030037","DOIUrl":"https://doi.org/10.3390/hemato2030037","url":null,"abstract":"Anaplastic large cell lymphoma (ALCL) is a histological subtype of non-Hodgkin lymphoma, largely characterized by anaplastic lymphoma kinase (ALK) positivity, resulting from the chromosomal translocation t(2;5). We report a pediatric case of ALK-positive ALCL with primary concomitant involvement of bone and central nervous system (CNS); thereafter, a literature review about pediatric primary bone and primary CNS ALCL was conducted. According to the analyzed data, our case is unique because it is characterized by the contemporary involvement of the spine and CNS. During and after chemotherapy, our patient was monitored by detecting minimal residual disease (MRD) through the analysis of fusion transcript nucleophosmin-ALK. MRD assessment, not only in bone marrow but also in peripheral blood, seems to be a very powerful tool for predicting the prognosis of pediatric ALCL patients, as already described in the literature. Moreover, as shown in our case, it could be used during the follow-up for early recognition of relapse.","PeriodicalId":93705,"journal":{"name":"Hemato","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45743907","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}
Plasmacytoid dendritic cells (PDC) constitute a small subset of normal bone marrow (BM) cells but have also been shown to be present, sometimes in large numbers, in several hematological malignancies such as acute myeloid leukemia with RUNX1 mutation, chronic myelomonocytic leukemia or, obviously, blastic plasmacytoid dendritic cell neoplasms. These cells have been reported to display somewhat variable immunophenotypic features in different conditions. However, little is known of their plasticity within individual patients. Using an unsupervised clustering tool (FlowSOM) to re-visit flow cytometry results of seven previously analyzed cases of hematological malignancies (6 acute myeloid leukemia and one chronic myelomonocytic leukemia) with a PDC contingent, we report here on the unexpectedly high variability of PDC subsets. Although five of the studied patients harbored a RUNX1 mutation, no consistent feature of PDCs could be disclosed as associated with this variant. Moreover, the one normal single-node small subset of PDC detected in the merged file of six normal BM could be retrieved in the remission BM samples of three successfully treated patients. This study highlights the capacity of unsupervised flow cytometry analysis to delineate cell subsets not detectable with classical supervised tools.
{"title":"The Plasmacytoid Dendritic Cell CD123+ Compartment in Acute Leukemia with or without RUNX1 Mutation: High Inter-Patient Variability Disclosed by Immunophenotypic Unsupervised Analysis and Clustering","authors":"A. Porwit, M. Béné","doi":"10.3390/hemato2030036","DOIUrl":"https://doi.org/10.3390/hemato2030036","url":null,"abstract":"Plasmacytoid dendritic cells (PDC) constitute a small subset of normal bone marrow (BM) cells but have also been shown to be present, sometimes in large numbers, in several hematological malignancies such as acute myeloid leukemia with RUNX1 mutation, chronic myelomonocytic leukemia or, obviously, blastic plasmacytoid dendritic cell neoplasms. These cells have been reported to display somewhat variable immunophenotypic features in different conditions. However, little is known of their plasticity within individual patients. Using an unsupervised clustering tool (FlowSOM) to re-visit flow cytometry results of seven previously analyzed cases of hematological malignancies (6 acute myeloid leukemia and one chronic myelomonocytic leukemia) with a PDC contingent, we report here on the unexpectedly high variability of PDC subsets. Although five of the studied patients harbored a RUNX1 mutation, no consistent feature of PDCs could be disclosed as associated with this variant. Moreover, the one normal single-node small subset of PDC detected in the merged file of six normal BM could be retrieved in the remission BM samples of three successfully treated patients. This study highlights the capacity of unsupervised flow cytometry analysis to delineate cell subsets not detectable with classical supervised tools.","PeriodicalId":93705,"journal":{"name":"Hemato","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42005906","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}
Chronic myelomonocytic leukemia (CMML) was named 50 years ago to describe a myeloid malignancy whose onset is typically insidious. This disease is now classified by the World Health Organisation as a myelodysplastic syndrome (MDS)-myeloproliferative neoplasm (MPN) overlap disease. Observed mostly in ageing people, CMML is characterized by the expansion of monocytes and, in many cases, granulocytes. Abnormal repartition of circulating monocyte subsets, as identified by flow cytometry, facilitates disease recognition. CMML is driven by the accumulation, in the stem cell compartment, of somatic variants in epigenetic, splicing and signaling genes, leading to epigenetic reprogramming. Mature cells of the leukemic clone contribute to creating an inflammatory climate through the release of cytokines and chemokines. The suspected role of the bone marrow niche in driving CMML emergence and progression remains to be deciphered. The clinical expression of the disease is highly diverse. Time-dependent accumulation of symptoms eventually leads to patient death as a consequence of physical exhaustion, multiple cytopenias and acute leukemia transformation. Fifty years after its identification, CMML remains one of the most severe chronic myeloid malignancies, without disease-modifying therapy. The proliferative component of the disease that distinguishes CMML from severe MDS has been mostly neglected. This review summarizes the progresses made in disease understanding since its recognition and argues for more CMML-dedicated clinical trials.
{"title":"Chronic Myelomonocytic Leukemia Gold Jubilee","authors":"E. Solary, R. Itzykson","doi":"10.3390/HEMATO2030026","DOIUrl":"https://doi.org/10.3390/HEMATO2030026","url":null,"abstract":"Chronic myelomonocytic leukemia (CMML) was named 50 years ago to describe a myeloid malignancy whose onset is typically insidious. This disease is now classified by the World Health Organisation as a myelodysplastic syndrome (MDS)-myeloproliferative neoplasm (MPN) overlap disease. Observed mostly in ageing people, CMML is characterized by the expansion of monocytes and, in many cases, granulocytes. Abnormal repartition of circulating monocyte subsets, as identified by flow cytometry, facilitates disease recognition. CMML is driven by the accumulation, in the stem cell compartment, of somatic variants in epigenetic, splicing and signaling genes, leading to epigenetic reprogramming. Mature cells of the leukemic clone contribute to creating an inflammatory climate through the release of cytokines and chemokines. The suspected role of the bone marrow niche in driving CMML emergence and progression remains to be deciphered. The clinical expression of the disease is highly diverse. Time-dependent accumulation of symptoms eventually leads to patient death as a consequence of physical exhaustion, multiple cytopenias and acute leukemia transformation. Fifty years after its identification, CMML remains one of the most severe chronic myeloid malignancies, without disease-modifying therapy. The proliferative component of the disease that distinguishes CMML from severe MDS has been mostly neglected. This review summarizes the progresses made in disease understanding since its recognition and argues for more CMML-dedicated clinical trials.","PeriodicalId":93705,"journal":{"name":"Hemato","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/HEMATO2030026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45972092","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}
Acute myeloid leukaemia (AML) is a haematological cancer with poor outcomes due to a lack of efficacious targeted therapies. The Nuclear Factor of Activated T Cells (NFAT) family of transcription factors is well characterised as a regulator of the cell cycle and differentiation in the myeloid lineage. Recent evidence has demonstrated that NFAT family members may have roles in regulating AML leukemogenesis and resistance to targeted therapy in myeloid leukaemia. Furthermore, gene expression data from patient samples show that some NFATs are more highly expressed in poorly differentiated AML and after disease relapse, implying that the NFAT family may have roles in specific types of AML. This review outlines the evidence for the role of NFAT in healthy myeloid tissue and explores how NFAT might regulate AML pathogenesis, highlighting the potential to target specific NFAT proteins therapeutically in AML.
{"title":"Transcriptional Regulation by the NFAT Family in Acute Myeloid Leukaemia","authors":"S. Patterson, Xu Huang, H. Jørgensen, A. Michie","doi":"10.3390/hemato2030035","DOIUrl":"https://doi.org/10.3390/hemato2030035","url":null,"abstract":"Acute myeloid leukaemia (AML) is a haematological cancer with poor outcomes due to a lack of efficacious targeted therapies. The Nuclear Factor of Activated T Cells (NFAT) family of transcription factors is well characterised as a regulator of the cell cycle and differentiation in the myeloid lineage. Recent evidence has demonstrated that NFAT family members may have roles in regulating AML leukemogenesis and resistance to targeted therapy in myeloid leukaemia. Furthermore, gene expression data from patient samples show that some NFATs are more highly expressed in poorly differentiated AML and after disease relapse, implying that the NFAT family may have roles in specific types of AML. This review outlines the evidence for the role of NFAT in healthy myeloid tissue and explores how NFAT might regulate AML pathogenesis, highlighting the potential to target specific NFAT proteins therapeutically in AML.","PeriodicalId":93705,"journal":{"name":"Hemato","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47964753","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}
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