Multilineage Dysplasia Is Associated with Worse Clinical Outcome Independent of the Diagnosis of Acute Myeloid Leukemia or Myelodysplastic Syndrome.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1440-1440 ◽  
Author(s):  
Hesham M. Amin ◽  
Sherry A. Pierce ◽  
Elihu H. Estey ◽  
Hagop M. Kantarjian ◽  
Susan M. O’Brien ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Myeloid Leukemia ◽  
Mitochondrial Membrane ◽  
Who Classification ◽  
Annexin V ◽  
Potential Analysis ◽  
Multilineage Dysplasia ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) and the myelodysplastic syndromes (MDS) comprise a heterogeneous group of hematopoietic neoplasms. The World Health Organization (WHO) classification includes the two new categories: AML with dysplasia in more than one lineage (multilineage dysplasia; MLD) and refractory cytopenia with MLD. However, the relevance of dysplasia in one lineage versus more than one lineage and the importance of separating MDS with MLD from AML with MLD are not known. We studied 1110 patients with AML and 171 patients with MDS classified according to the WHO criteria and treated at MD Anderson Cancer Center from 1995 to 2003. All MDS patients had advanced disease requiring treatment and included 19 patients with refractory anemia (RA), 7 with RA with ringed sideroblasts (RARS), and 145 with RA with excess blasts (RAEB). Survival analysis showed no statistical significance in overall survival between MDS patients and AML patients when classified according to the WHO classification (P=0.196). When AML and MDS patients were considered as one group, but divided based on the presence or absence of MLD, patients with MLD had significantly shorter survival (P=.004; Figure 1). More importantly, multivariate Cox proportional hazard model showed that the shorter survival in the combined AML and MDS patients with MLD was independent of cytogenetic abnormalities, antecedent hematologic disease, performance status, and the original diagnosis of AML or MDS. As expected, shorter survival was found in AML patients with MLD as compared with those with no dysplasia or dysplasia of one lineage (P=.003). The presence of dysplasia in one lineage was irrelevant for the clinical course. Apoptosis detection using annexin V staining or mitochondrial membrane potential analysis showed significantly higher apoptosis in AML patients with MLD as compared with those patients without MLD and the presence of increased apoptosis correlated with shorter survival (P=.04). The present study demonstrates that the criteria established by the WHO classification for the diagnosis of AML and MDS can be significantly enhanced if the presence or absence of MLD is considered irrespective of the percentage of blasts. Furthermore, apoptosis can be detected in AML and MDS patients using annexin V staining or mitochondrial membrane potential analysis and it can be utilized to indirectly reflect the level of dysplasia in these patients. With the progress in targeted therapy, the classification of leukemia and myelodysplasia based on biological abnormalities may provide more helpful clues for therapy and clinical management. Figure Figure

Clinical Characterization of Acute Myeloid Leukemia with Myelodysplasia-Related Changes as Defined by the 2008 WHO Classification System.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 922-922
Author(s):  
Olga K Weinberg ◽  
Mahesh Seetharam ◽  
Li Ren ◽  
Lisa Ma ◽  
Katie Seo ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Clinical Outcome ◽  
Myeloid Leukemia ◽  
Who Classification ◽  
Risk Group ◽  
Who Criteria ◽  
Multilineage Dysplasia ◽  
Acute Myeloid

Abstract Background: Although some studies have validated the 2001 WHO classification of acute myeloid leukemia (AML), including the importance of multilineage dysplasia, others have suggested that multilineage dysplasia correlates with unfavorable cytogenetics but has no independent impact on prognosis. In 2008, the revised WHO classification system has expanded this category into “AML with myelodysplasia-related changes” (AML-MRC) that now includes 1) AML arising from myelodysplastic syndrome (MDS), 2) AML with MDS-related cytogenetic abnormalities, and 3) AML with multilineage dysplasia. An individual case may fall into this category by meeting any of the criteria. The goal of the current study is to clinically characterize this newly defined AML-MRC subgroup. Methods: One-hundred consecutive AML patients diagnosed at Stanford University Hospital between 2005 and 2007 with adequate material for mutation analysis were studied. Cases were classified using the 2008 WHO criteria. Diagnostic cytogenetic findings were reviewed and patients were stratified into risk groups using Southwest Oncology Group criteria. Available flow cytometry immunophenotyping results were reviewed and all samples were tested for NPM, FLT3 (ITD and D835) and CEBPA mutations. Clinical parameters including hemogram data at time of diagnosis were reviewed. Clinical follow-up including overall survival (OS), progression free survival (PFS) and complete remission (CR) rates were retrospectively determined. Kaplan-Meier methods and univariate and multivariate Cox proportional hazards regression analysis were used to compare the clinical data. Results: The cases included 57 males and 43 females with a median age of 56 (range 17–81). Cytogenetic risk-group stratification resulted in 9 patients with favorable, 65 with intermediate and 19 with unfavorable risk status. Using the 2008 WHO criteria, there were 48 AML-MRC, 40 AML not otherwise specified (AML-NOS), 9 AML with either t(8;21), inv(16) or t(15;17), and 3 therapy related AMLs. Overall, 26 patients had a NPM1 mutation (16 of which were FLT3 mutated), 25 had FLT3-ITD, 8 had FLT3-D835 and 9 had a CEBPA mutation (3 of which were FLT3 mutated). Compared to AML-NOS, patients with AML-MRC were significantly older (59 vs 51 years, p=0.014) and presented with lower hemoglobin (9 vs 11.2 g/dL, p=0.044), lower platelets (47 vs 54 K/uL, p=0.059), unfavorable cytogenetics (14/46 vs 3/36, p=0.014) and exhibited a decreased frequency of CEBPA mutation (0/46 vs 7/40, p=0.001) as compared to AML-NOS. Based on the flow cytometry immunophenotyping, the blasts from patients with AML-MRC more frequently expressed CD14 compared to AML-NOS (10/46 vs 4/36, p=0.048). Clinical outcome data showed that patients with AML-MRC had a significantly worse OS, PFS and CR compared to AML-NOS (Figure, all p<0.0001). Even after excluding the 14 patients with unfavorable cytogenetics from the AML-MRC group, the remaining patients with AML-MRC (defined solely by the presence of multilineage dysplasia) had worse outcomes compared to all AML-NOS patients (OS, p=0.013; PFS, p=0.012; CR, p=0.0076). Among 65 patients with intermediate risk cytogenetics, the outcome difference between the AML-MRC and AML-NOS groups remained significant (OS, p=0.0292; PFS, p=0.0232), also indicating prognostic significance of multilineage dysplasia. Within the AML-MRC group, univariate analysis showed that low platelets (<20,000/mm3), FLT3-D835 mutation and MDS-related cytogenetics correlated with OS (p=0.0456, p=0.0265, p=0.002 respectively) and PFS (p=0.0478, p=0.0626, p=0.001). A multivariate Cox proportional hazard analysis, performed on the entire group, identified unfavorable cytogenetic risk group, advanced age (> 60), FLT3-ITD and AML-MRC status as significant predictors of worse OS with the following respective hazard ratios: 2.82 (95% CI, 1.52–5.26), 2.11 (1.01–4.42), 1.98 (1.01–3.90), 1.92 (1.01–3.65). Conclusion: The newly defined WHO category of AML-MRC exhibits a significantly worse clinical outcome compared to AML-NOS and is predictive of worse overall survival in the multivariate analysis of AML patients, independent of age or cytogenetic risk group. These findings support the clinical, morphologic and cytogenetic criteria for this 2008 WHO AML category. Figure Figure

Clinical characterization of acute myeloid leukemia with myelodysplasia-related changes as defined by the 2008 WHO classification system

Blood ◽  
2009 ◽  
Vol 113 (9) ◽  
pp. 1906-1908 ◽  
Author(s):  
Olga K. Weinberg ◽  
Mahesh Seetharam ◽  
Li Ren ◽  
Katie Seo ◽  
Lisa Ma ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Who Classification ◽  
Progression Free Survival ◽  
World Health ◽  
Multilineage Dysplasia ◽  
Molecular Features ◽  
Not Otherwise Specified ◽  
Cebpa Mutations ◽  
Acute Myeloid

Although some studies have validated the 2001 World Health Organization (WHO) classification of acute myeloid leukemia (AML), including the importance of multilineage dysplasia, others have suggested that multilineage dysplasia correlates with unfavorable cytogenetics but has no independent impact on prognosis. In 2008, the revised WHO classification has expanded this category into “AML with myelodysplasia-related changes” (AML-MRC). We evaluated the clinical, pathologic, cytogenetic, and molecular features of 100 AML patients using the 2008 WHO criteria. Patients underwent genetic screening for NPM1, FLT3-ITD, FLT3-D835, and CEBPA mutations. Compared with patients with AML, not otherwise specified, patients with AML-MRC were significantly older (P = .014), presented with a lower hemoglobin (P = .044), more frequently expressed CD14 (P = .048), and exhibited a decreased frequency of CEBPA mutations (P = .001). Multivariate analysis indicated that patients with AML-MRC had a significantly worse overall survival, progression-free survival, and complete response compared with AML-not otherwise specified (all P < .001). These data support the clinical, morphologic, and cytogenetic criteria for this 2008 WHO AML category.

Myelodysplasia-Related Changes Have Adverse Prognostic Significance in Children with Acute Myeloid Leukemia; A Report From the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG).

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2583-2583
Author(s):  
Akitoshi Kinoshita ◽  
Hayato Miyachi ◽  
Hiromichi Matsushita ◽  
Miharu Yabe ◽  
Tomohiko Taki ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Who Classification ◽  
Prognostic Significance ◽  
Morphological Features ◽  
Review System ◽  
Free Survival ◽  
Multilineage Dysplasia ◽  
Acute Myeloid

Abstract Abstract 2583 Background: The 2008 WHO classification expanded the category of acute myeloid leukemia (AML) with multilineage dysplasia of the 2001 WHO classification into AML with myelodysplasia-related changes (AML-MRC). Although AML with multilineage dysplasia (AML-MLD) is diagnosed based on morphological features alone, AML-MRC includes AML with a previous history of myelodysplastic syndrome or myeloproliferative neoplasms and AML with a myelodysplasia-related cytogenetic abnormality as well as AML-MLD. Since this category of AML has been believed to be rare in children, its clinical impact on children remains unknown. We developed a comprehensive and prospective central review system in a clinical trial for pediatric AML, in which unexpected high incidence of AML-MRC was found. Thus, we evaluated the clinical characteristics and prognostic significance of AML-MRC in children. Patients & Methods: JPLSG AML-05, registered at http://www.umin.ac.jp/ctr/as UMIN000000511, is a nation-wide multi-institutional study for children (age <18 years) with de novo AML from 11/1/2006 to 12/31/2010 (acute promyelocytic leukemia and myeloid leukemia associated with Down syndrome excluded). On the trial, morphology was prospectively diagnosed by a central review system. A diagnosis of AML-MLD was made by the presence of dysplasia in 50% or more of the cells in 2 or more lineages. Cytogenetic tests were carried out in regional laboratories, but reports were reviewed centrally. Mutations of FLT3 were examined for all patients. Results: Among 447 eligible patients recruited, a total of 93 patients (20.8%) were diagnosed as AML-MRC; 34 from morphological features, 65 from myelodysplasia-related cytogenetic abnormalities and six from the both. The cases with AML-MRC included 48 boys and 45 girls with a median age of 3 years (range; 0–17 years). Ten patients with AML-MRC had FLT3-internal tandem duplication (ITD). Three-year probability of event-free survival (3y-pEFS) and 3-year probability of overall survival (3y-pOS) at the 93 patients was 37.1% (95%CI, 26.9 – 47.3%) and 56.8% (95%CI, 45.2 – 66.8%), respectively. The median follow-up of alive patients as of May 2012 was 3.4 years (range;1.3–5.3 years). Comparison of the clinical outcome of AML-MRC with AML, not otherwise specified (AML-NOS)(n=111), showed that AML-MRC had a lower complete remission rate after two induction courses(67.7% vs 85.6%, p<0.01), and worse 3y-pEFS (37.1% vs 53.8%, p= 0.02), but that 3y-pOS (56.8% vs 68.9%, p= 0.05) and 3 year probability of relapse-free survival after achieving complete remission (46.9.% vs 62.8%, p= 0.06) were similar. Although no differences were seen in sex and WBC count at diagnosis between AML-MRC and AML-NOS, the median age or the incidence of FLT3-ITD positivity of AML-MRC was lower than that of AML-NOS. In Cox regression analysis, adjusted hazard ratio (HR) of patients diagnosed with AML-MRC for EFS was significantly worse compared to those diagnosed with AML-NOS after controlling for these baseline patients and disease characteristics (HR 1.7,p<0.01). Conclusions: Our study suggests that AML-MRC is not rare in children. AML-MRC had adverse prognostic significance in children partly due to the low induction rate. Induction chemotherapy awaits further improvement for children with AML-MRC. Disclosures: No relevant conflicts of interest to declare.

High Mitochondrial Membrane Potential Identifies Patients with Myeloproliferative Neoplasms with a More Aggressive Natural History

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1992-1992
Author(s):  
Jeffrey R Gardner ◽  
Omar Abdel-Wahab ◽  
Mark Frattini ◽  
Joseph G Jurcic ◽  
Kristina Knapp ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Polycythemia Vera ◽  
Mitochondrial Membrane Potential ◽  
Essential Thrombocythemia ◽  
Blood Cells ◽  
Myeloid Leukemia ◽  
Mitochondrial Membrane ◽  
Myeloproliferative Neoplasms ◽  
Primary Myelofibrosis ◽  
Acute Myeloid

Abstract Abstract 1992 The myeloproliferative neoplasms (MPN) can have a variable natural history. Polycythemia vera and essential thrombocythemia, in particular, are conditions that can extend over decades, but some patients have clinical progression to myelofibrosis or acute myeloid leukemia. As first articulated by Warburg, cancers are metabolically distinguished from normal tissues by the use of glycolysis under aerobic conditions. To metabolically characterize the blood cells of patients with myeloproliferative neoplasms, we measured the mitochondrial membrane potential using the cyanine dye, JC-1. In examining cells derived from the blood and/or marrow of 159 patients with primary myelofibrosis, polycythemia vera and essential thrombocythemia, we found that the mitochondrial membrane potential (FL2/FL1=electrochemical potential/mitochondrial mass) was elevated compared to the blood cells of normal individuals. Thirty five percent of patients with polycythemia vera and essential thrombocythemia had normal MMP. In contrast, 97% of patients with primary myelofibrosis, post-polycythemia myelofibrosis, post-essential thrombocythemia myelofibrosis and acute myeloid leukemia following an MPN had evidence of cell populations with higher mitochondrial membrane potential. Cells with distinctly higher mitochondrial membrane potential could be indentified in platelets and polymorphonuclear leukocytes; however the MMP of lymphocytes was normal, indicating that the alteration in metabolic state likely occurred in a multipotential myeloid stem cell. Cell populations were confirmed by co-staining with anti-CD19, -CD45, -GlycophorinA and -β3-integrin antibodies. Sequential analysis of patient samples found that the acquisition of higher mitochondrial membrane potential was stable and persistent over 2 years or more of follow up and that elevated membrane potential predisposed patients to disease progression. The balance of patients (65%) with ET had evidence of increased MMP suggesting the possibility of disease in an early state of evolution to a more aggressive condition. The increased MMP did not correlate with the presence of mutation in JAK2. These results indicate that clinically advanced MPN can be characterized by changes in mitochondrial physiology that might be identified non-invasively by flow cytometric staining with JC-1. In addition, the early nature of these changes may help to identify therapeutic targets. Disclosures: No relevant conflicts of interest to declare.

Comprehensive Analysis of Genetic Alterations in Acute Myeloid Leukemia According to the WHO Classification.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4311-4311
Author(s):  
Yuichi Ishikawa ◽  
Hitoshi Kiyoi ◽  
Akane Tsujimura ◽  
Yasusi Miyazaki ◽  
Masao Tomonaga ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Who Classification ◽  
Normal Karyotype ◽  
Genetic Alterations ◽  
P53 Mutation ◽  
Npm1 Mutation ◽  
Multilineage Dysplasia ◽  
Genetic Abnormalities ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) is a heterogeneous clonal disorder of hematopoietic progenitor cells, and is thought to be the consequence of two broad complementation classes of mutations: those that confer a proliferative and/or survival advantage to hematopoietic progenitors, and those that impair hematopoietic differentiation and confer properties of self-renewal. To date, several genetic alterations, which are involved in the pathophysiology of the AML development, have been apparent, and some of them have been disclosed to have an impact on the clinical management. Therefore, it is required to establish the detailed classification of AML according to the genetic status. In this study, we comprehensively analyzed the genetic alterations in AML patients in comparison with the WHO classification. The study population included 115 newly diagnosed AML patients consisting of 25 recurrent genetic abnormalities, 25 multilineage dysplasia, 7 therapy-related and 56 not otherwise categorized WHO subcategories. Bone marrow samples were obtained from the patients after obtaining informed consent for banking and molecular analyses. Mutations in FLT3, cKIT, NPM1, N-RAS, p53, C/EBPa, AML1 and AKT1 genes were analyzed as previously described. In consistent with previous reports, FLT3 (20.9%), NPM1 (14.8%) and C/EBPa (13.0%) mutations were frequently observed, while no AKT1 mutation was found. Furthermore, NPM1 mutation was not found in AML with recurrent genetic abnormalities and C/EBPa mutation was not found in AML with recurrent genetic abnormalities or therapy related. Nine cases have double mutations of FLT3 and NPM1 genes, and 3 have FLT3 and C/EBPa mutations. Of note is that 15 of 25 (60%) AML with multilineage dysplasia cases have at least one mutation in p53, NPM1, C/EBPa, FLT3, N-RAS and AML1 genes and that p53 mutation was selectively found in the cases with complex karyotype. However, 4 AML with multilineage dysplasia cases with normal karyotype did not have any mutations in the analyzed genes. Comprehensive genetic analysis clarifies the detailed molecular base of AML and could make the subdivision of the WHO classification by combining the analysis for clinical impacts. Especially, mutation status in p53, NPM1 and C/EBPa genes seems to be useful for the subdivision of the AML with multilineage dysplasia, which is the most heterogeneous subcategory in the WHO classification.

Synthesis and Biological Evaluation of Novel Heterocyclic Imines Linked Coumarin- Thiazole Hybrids as Anticancer Agents

2019 ◽  
Vol 19 (4) ◽  
pp. 557-566 ◽  
Author(s):  
Nerella S. Goud ◽  
Mahammad S. Ghouse ◽  
Jatoth Vishnu ◽  
Jakkula Pranay ◽  
Ravi Alvala ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Membrane Potential ◽  
Fluorescence Spectroscopy ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Annexin V ◽  
Biological Evaluation ◽  
Dependent Manner ◽  
Dapi Staining ◽  
Dose Dependent

Background: Human Galectin-1, a protein of lectin family showing affinity towards β-galactosides has emerged as a critical regulator of tumor progression and metastasis, by modulating diverse biological events including homotypic cell aggregation, migration, apoptosis, angiogenesis and immune escape. Therefore, galectin-1 inhibitors might represent novel therapeutic agents for cancer. Methods: A new series of heterocyclic imines linked coumarin-thiazole hybrids (6a-6r) was synthesized and evaluated for its cytotoxic potential against a panel of six human cancer cell lines namely, lung (A549), prostate (DU-145), breast (MCF-7 & MDA-MB-231), colon (HCT-15 & HT-29) using MTT assay. Characteristic apoptotic assays like DAPI staining, cell cycle, annexin V and Mitochondrial membrane potential studies were performed for the most active compound. Furthermore, Gal-1 inhibition was confirmed by ELISA and fluorescence spectroscopy. Results: Among all, compound 6g 3-(2-(2-(pyridin-2-ylmethylene) hydrazineyl) thiazol-4-yl)-2H-chromen-2- one exhibited promising growth inhibition against HCT-15 colorectal cancer cells with an IC50 value of 1.28 ± 0.14 µM. The characteristic apoptotic morphological features like chromatin condensation, membrane blebbing and apoptotic body formation were clearly observed with compound 6g on HCT-15 cells using DAPI staining studies. Further, annexin V-FITC/PI assay confirmed effective early apoptosis induction by treatment with compound 6g. Loss of mitochondrial membrane potential and enhanced ROS generation were confirmed with JC-1 and DCFDA staining method, respectively by treatment with compound 6g, suggesting a possible mechanism for inducing apoptosis. Moreover, flow cytometric analysis revealed that compound 6g blocked G0/G1 phase of the cell cycle in a dose-dependent manner. Compound 6g effectively reduced the levels of Gal-1 protein in a dose-dependent manner. The binding constant (Ka) of 6g with Gal-1 was calculated from the intercept value which was observed as 1.9 x 107 M-1 by Fluorescence spectroscopy. Molecular docking studies showed strong interactions of compound 6g with Gal-1 protein. Conclusion: Our studies demonstrate the anticancer potential and Gal-1 inhibition of heterocyclic imines linked coumarin-thiazole hybrids.

scholarly journals Inhibition of EZH2 by chidamide exerts antileukemia activity and increases chemosensitivity through Smo/Gli-1 pathway in acute myeloid leukemia

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xuejie Jiang ◽  
Ling Jiang ◽  
Jiaying Cheng ◽  
Fang Chen ◽  
Jinle Ni ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Histone Deacetylases ◽  
Myeloid Leukemia ◽  
Hdac Inhibitors ◽  
Annexin V ◽  
Fluorescein Isothiocyanate ◽  
Gli 1 ◽  
Acute Myeloid

Abstract Background Epigenetic dysregulation plays important roles in leukemogenesis and the progression of acute myeloid leukemia (AML). Histone acetyltransferases (HATs) and histone deacetylases (HDACs) reciprocally regulate the acetylation and deacetylation of nuclear histones. Aberrant activation of HDACs results in uncontrolled proliferation and blockade of differentiation, and HDAC inhibition has been investigated as epigenetic therapeutic strategy against AML. Methods Cell growth was assessed with CCK-8 assay, and apoptosis was evaluated by flow cytometry in AML cell lines and CD45 + and CD34 + CD38- cells from patient samples after staining with Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI). EZH2 was silenced with short hairpin RNA (shRNA) or overexpressed by lentiviral transfection. Changes in signaling pathways were detected by western blotting. The effect of chidamide or EZH2-specific shRNA (shEZH2) in combination with adriamycin was studied in vivo in leukemia-bearing nude mouse models. Results In this study, we investigated the antileukemia effects of HDAC inhibitor chidamide and its combinatorial activity with cytotoxic agent adriamycin in AML cells. We demonstrated that chidamide suppressed the levels of EZH2, H3K27me3 and DNMT3A, exerted potential antileukemia activity and increased the sensitivity to adriamycin through disruption of Smo/Gli-1 pathway and downstream signaling target p-AKT in AML cells and stem/progenitor cells. In addition to decreasing the levels of H3K27me3 and DNMT3A, inhibition of EZH2 either pharmacologically by chidamide or genetically by shEZH2 suppressed the activity of Smo/Gli-1 pathway and increased the antileukemia activity of adriamycin against AML in vitro and in vivo. Conclusions Inhibition of EZH2 by chidamide has antileukemia activity and increases the chemosensitivity to adriamycin through Smo/Gli-1 pathway in AML cells (Fig. 5). These findings support the rational combination of HDAC inhibitors and chemotherapy for the treatment of AML.

Acute Leukemia

2016 ◽  
Author(s):  
Richard A. Larson ◽  
Roland B Walter
Keyword(s):  
Acute Myeloid Leukemia ◽  
Acute Lymphoblastic Leukemia ◽  
Acute Leukemia ◽  
Myeloid Leukemia ◽  
Who Classification ◽  
Lymphoblastic Leukemia ◽  
World Health ◽  
Acute Leukemias ◽  
Acute Myeloid

The acute leukemias are malignant clonal disorders characterized by aberrant differentiation and proliferation of transformed hematopoietic progenitor cells. These cells accumulate within the bone marrow and lead to suppression of the production of normal blood cells, with resulting symptoms from varying degrees of anemia, neutropenia, and thrombocytopenia or from infiltration into tissues. They are currently classified by their presumed cell of origin, although the field is moving rapidly to genetic subclassification. This review covers epidemiology; etiology; classification of leukemia by morphology, immunophenotyping, and cytogenetic/molecular abnormalities; cytogenetics of acute leukemia; general principles of therapy; acute myeloid leukemia; acute lymphoblastic leukemia; and future possibilities. The figure shows the incidence of acute leukemias in the United States. Tables list World Health Organization (WHO) classification of acute myeloid leukemia and related neoplasms, expression of cell surface and cytoplasmic markers for the diagnosis of acute myeloid leukemia and mixed-phenotype acute leukemia, WHO classification of acute lymphoblastic leukemia, WHO classification of acute leukemias of ambiguous lineage, WHO classification of myelodysplastic syndromes, European LeukemiaNet cytogenetic and molecular genetic subsets in acute myeloid leukemia with prognostic importance, cytogenetic and molecular subtypes of acute lymphoblastic leukemia, terminology used in leukemia treatment, and treatment outcome for adults with acute leukemia. This review contains 1 highly rendered figure, 9 tables, and 117 references.

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