Browsing by Subject "Acute myeloid leukemia"
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Item Acute appendicitis caused by acute myeloid leukemia(Wiley, 2014-10) Zhang, Shanxiang; Chen, Shaoxiong; Pathology & Laboratory Medicine, School of MedicineKEY CLINICAL MESSAGE: A case of appendiceal involvement by acute myeloid leukemia (AML) in an adult with recent history of AML transformed from myelodysplastic syndrome (MDS) was presented. Being aware of this rare presentation in particular in a patient with history of MDS and/or AML is important for prompt clinical diagnosis and management.Item Acute Myeloid Leukemia: The Aga Khan Experience(Association of Kenya Physicians, 2007) Ngunga, Mzee; Association of Kenya Physicians Scientific Conference (11th : Mar. 2007 : Eldoret, Kenya)AML is characterized by an increase in the number of myeloid cells in the marrow and an arrest in their maturation.Item Automated Assessment of Disease Progression in Acute Myeloid Leukemia by Probabilistic Analysis of Flow Cytometry Data(Institute of Electrical and Electronics Engineers, 2017-05) Rajwa, Bartek; Wallace, Paul K.; Griffiths, Elizabeth A.; Dundar, Murat; Computer and Information Science, School of ScienceOBJECTIVE: Flow cytometry (FC) is a widely acknowledged technology in diagnosis of acute myeloid leukemia (AML) and has been indispensable in determining progression of the disease. Although FC plays a key role as a posttherapy prognosticator and evaluator of therapeutic efficacy, the manual analysis of cytometry data is a barrier to optimization of reproducibility and objectivity. This study investigates the utility of our recently introduced nonparametric Bayesian framework in accurately predicting the direction of change in disease progression in AML patients using FC data. METHODS: The highly flexible nonparametric Bayesian model based on the infinite mixture of infinite Gaussian mixtures is used for jointly modeling data from multiple FC samples to automatically identify functionally distinct cell populations and their local realizations. Phenotype vectors are obtained by characterizing each sample by the proportions of recovered cell populations, which are, in turn, used to predict the direction of change in disease progression for each patient. RESULTS: We used 200 diseased and nondiseased immunophenotypic panels for training and tested the system with 36 additional AML cases collected at multiple time points. The proposed framework identified the change in direction of disease progression with accuracies of 90% (nine out of ten) for relapsing cases and 100% (26 out of 26) for the remaining cases. CONCLUSIONS: We believe that these promising results are an important first step toward the development of automated predictive systems for disease monitoring and continuous response evaluation. SIGNIFICANCE: Automated measurement and monitoring of therapeutic response is critical not only for objective evaluation of disease status prognosis but also for timely assessment of treatment strategies.Item CNS involvement in AML at diagnosis is rare and does not affect response or survival: data from 11 ECOG-ACRIN trials(American Society of Hematology, 2021) Ganzel, Chezi; Lee, Ju-Whei; Fernandez, Hugo F.; Paietta, Elisabeth M.; Luger, Selina M.; Lazarus, Hillard M.; Cripe, Larry D.; Douer, Dan; Wiernik, Peter H.; Rowe, Jacob M.; Tallman, Martin S.; Litzow, Mark R.; Medicine, School of MedicineCentral nervous system (CNS) involvement in patients with newly diagnosed acute myeloid leukemia (AML) is rare, and systematic data regarding outcome are scarce. This retrospective study summarized data from 11 consecutive Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) clinical trials for patients with newly diagnosed AML. In all, 3240 patients with AML were analyzed, and 36 (1.11%) were found to have CNS involvement at diagnosis. The incidence of CNS disease among the 5 studies with per protocol mandatory lumbar puncture (LP) was similar to the incidence among studies in which LP was performed at the discretion of the investigator (0.86% vs 1.41%; P = .18). There was no significant difference in the rate of complete remission (CR) among patients with CNS involvement and those with other extramedullary disease (EMD) sites or those with no EMD (52.8% vs 59.3%-60%). The median overall survival (OS) for patients who were CNS positive, who had other EMD, or who had no EMD was 11.4, 11.3, and 12.7 months, respectively. There was no difference in OS among patients with CNS involvement, those with other EMD (hazard ratio [HR], 0.96; adjusted P = .84), and those with no EMD (HR, 1.19; adjusted P = .44). In conclusion, the reported incidence of CNS involvement in patients with newly diagnosed AML is low (1.1%), irrespective of whether an LP is mandatory or not. The presence of CNS disease at diagnosis in and of itself does not seem to portend a poor prognosis for achieving an initial CR or for OS.Item Comorbidity, Physical Function, and Quality of Life in Older Adults with Acute Myeloid Leukemia(Springer, 2017-12) Storey, Susan; Gray, Tamryn Fowler; Bryant, Ashley Leak; School of NursingPurpose of review: To describe the pathology, impact of comorbidities, functional limitations, symptoms, and quality of life (QOL) related to treatment of acute myeloid leukemia (AML) in older adults. Recent findings: AML is a rare aggressive hematologic disease that occurs most often in older adults. The prognosis for older patients with AML is markedly worse due to genetic mutations and patient characteristics such as comorbidities and functional limitations. Patient characteristics may influence treatment decisions, as well as impact symptoms, functional ability, health-related outcomes and (QOL). Summary: As the population continues to age, the number of people diagnosed with AML is expected to increase. Better management of comorbidities is imperative to improving QOL and other treatment related outcomes. Prospective, longitudinal and multi-site studies are warranted to further understand the interaction between these characteristics on symptoms, outcomes and QOL.Item Comparative Analysis of AML Classification Systems: Evaluating the WHO, ICC, and ELN Frameworks and Their Distinctions(MDPI, 2024-08-22) Salman, Huda; Medicine, School of MedicineComprehensive analyses of the molecular heterogeneity of acute myelogenous leukemia, AML, particularly when malignant cells retain normal karyotype, has significantly evolved. In 2022, significant revisions were introduced in the World Health Organization (WHO) classification and the European LeukemiaNet (ELN) 2022 guidelines of acute myeloid leukemia (AML). These revisions coincided with the inception of the first version of the International Consensus Classification (ICC) for AML. These modifications aim to improve diagnosis and treatment outcomes via a comprehensive incorporation of sophisticated genetic and clinical parameters as well as facilitate accruals to innovative clinical trials. Key updates include modifications to the blast count criteria for AML diagnosis, with WHO 2022 eliminating the ≥20% blast requirement in the presence of AML-defining abnormalities and ICC 2022 setting a 10% cutoff for recurrent genetic abnormalities. Additionally, new categories, such as AML with mutated TP53 and MDS/AML, were introduced. ELN 2022 guidelines retained risk stratification approach and emphasized the critical role of measurable residual disease (MRD) that increased the use of next-generation sequencing (NGS) and flow cytometry testing. These revisions underscore the importance of precise classification for targeted treatment strategies and improved patient outcomes. How much difference versus concordance these classifications present and the impact of those on clinical practice is a continuing discussion.Item HoxA9 binds and represses the Cebpa +8 kb enhancer(PLOS, 2019-05-23) Peng, Lei; Guo, Hong; Ma, Peilin; Sun, Yuqing; Dennison, Lauren; Aplan, Peter D.; Hess, Jay L.; Friedman, Alan D.; Pathology and Laboratory Medicine, School of MedicineC/EBPα plays a key role in specifying myeloid lineage development. HoxA9 is expressed in myeloid progenitors, with its level diminishing during myeloid maturation, and HOXA9 is over-expressed in a majority of acute myeloid leukemia cases, including those expressing NUP98-HOXD13. The objective of this study was to determine whether HoxA9 directly represses Cebpa gene expression. We find 4-fold increased HoxA9 and 5-fold reduced Cebpa in marrow common myeloid and LSK progenitors from Vav-NUP98-HOXD13 transgenic mice. Conversely, HoxA9 decreases 5-fold while Cebpa increases during granulocytic differentiation of 32Dcl3 myeloid cells. Activation of exogenous HoxA9-ER in 32Dcl3 cells reduces Cebpa mRNA even in the presence of cycloheximide, suggesting direct repression. Cebpa transcription in murine myeloid cells is regulated by a hematopoietic-specific +37 kb enhancer and by a more widely active +8 kb enhancer. ChIP-Seq analysis of primary myeloid progenitor cells expressing exogenous HoxA9 or HoxA9-ER demonstrates that HoxA9 localizes to both the +8 kb and +37 kb Cebpa enhancers. Gel shift analysis demonstrates HoxA9 binding to three consensus sites in the +8 kb enhancer, but no affinity for the single near-consensus site present in the +37 kb enhancer. Activity of a Cebpa +8 kb enhancer/promoter-luciferase reporter in 32Dcl3 or MOLM14 myeloid cells is increased ~2-fold by mutation of its three HOXA9-binding sites, suggesting that endogenous HoxA9 represses +8 kb Cebpa enhancer activity. In contrast, mutation of five C/EBPα-binding sites in the +8 kb enhancer reduces activity 3-fold. Finally, expression of a +37 kb enhancer/promoter-hCD4 transgene reporter is reduced ~2-fold in marrow common myeloid progenitors when the Vav-NUP98-HOXD13 transgene is introduced. Overall, these data support the conclusion that HoxA9 represses Cebpa expression, at least in part via inhibition of its +8 kb enhancer, potentially allowing normal myeloid progenitors to maintain immaturity and contributing to the pathogenesis of acute myeloid leukemia associated with increased HOXA9.Item Inhibition of BCL2A1 by STAT5 inactivation overcomes resistance to targeted therapies of FLT3-ITD/D835 mutant AML(Elsevier, 2022) Yamatani, Kotoko; Ai, Tomohiko; Saito, Kaori; Suzuki, Koya; Hori, Atsushi; Kinjo, Sonoko; Ikeo, Kazuho; Ruvolo, Vivian; Zhang, Weiguo; Mak, Po Yee; Kaczkowski, Bogumil; Harada, Hironori; Katayama, Kazuhiro; Sugimoto, Yoshikazu; Myslinski, Jered; Hato, Takashi; Miida, Takashi; Konopleva, Marina; Hayashizaki, Yoshihide; Carter, Bing Z.; Tabe, Yoko; Andreeff, Michael; Medicine, School of MedicineTyrosine kinase inhibitors (TKIs) are established drugs in the therapy of FLT3-ITD mutated acute myeloid leukemia (AML). However, acquired mutations, such as D835 in the tyrosine kinase domain (FLT3-ITD/D835), can induce resistance to TKIs. A cap analysis gene expression (CAGE) technology revealed that the gene expression of BCL2A1 transcription start sites was increased in primary AML cells bearing FLT3-ITD/D835 compared to FLT3-ITD. Overexpression of BCL2A1 attenuated the sensitivity to quizartinib, a type II TKI, and venetoclax, a selective BCL2 inhibitor, in AML cell lines. However, a type I TKI, gilteritinib, inhibited the expression of BCL2A1 through inactivation of STAT5 and alleviated TKI resistance of FLT3-ITD/D835. The combination of gilteritinib and venetoclax showed synergistic effects in the FLT3-ITD/D835 positive AML cells. The promoter region of BCL2A1 contains a BRD4 binding site. Thus, the blockade of BRD4 with a BET inhibitor (CPI-0610) downregulated BCL2A1 in FLT3-mutated AML cells and extended profound suppression of FLT3-ITD/D835 mutant cells. Therefore, we propose that BCL2A1 has the potential to be a novel therapeutic target in treating FLT3-ITD/D835 mutated AML.Item Integrative analysis identifies an older female-linked AML patient group with better risk in ECOG-ACRIN Cancer Research Group's clinical trial E3999(Springer Nature, 2022-09-23) Rapaport, Franck; Seier, Kenneth; Neelamraju, Yaseswini; Hassane, Duane; Baslan, Timour; Gildea, Daniel T.; Haddox, Samuel; Lee, Tak; Murdock, H. Moses; Sheridan, Caroline; Thurmond, Alexis; Wang, Ling; Carroll, Martin; Cripe, Larry D.; Fernandez, Hugo; Mason, Christopher E.; Paietta, Elisabeth; Roboz, Gail J.; Sun, Zhuoxin; Tallman, Martin S.; Zhang, Yanming; Gönen, Mithat; Levine, Ross; Melnick, Ari M.; Kleppe, Maria; Garrett-Bakelman, Francine E.; Medicine, School of MedicineItem Malyglycemia and health outcomes in hospitalized patients with acute myleoid leukemia(2015-04-09) Storey, Susan; Von Ah, Diane Marie; McDaniel, Anna; Ebright, Patricia R.; Weaver, Michael TimothyAcute Myeloid Leukemia (AML) is the most common hematologic malignancy. Malglycemia is a disorder of glucose metabolism and includes hyperglycemia, hypoglycemia and the combination of hyperglycemia and hypoglycemia. Malglycemia has been shown to occur frequently during hospitalization among critical care patients and has been associated with increased risk of sepsis and mortality. Little is known, however, about the prevalence and role of malglycemia on the health outcomes of AML patients hospitalized for initial induction therapy. Malglycemia may be of particular importance to the patient with AML because, researchers have found that malglycemia may promote cellular changes which facilitate the progression of cancer, alter treatment response, and attenuate immune response. The purpose of this study was to determine the prevalence of malglycemia (hyperglycemia, hypoglycemia or the combination) and to examine its role on a comprehensive set of health outcomes (neutropenic days, infection, and septicemia, and sepsis, induction hospital length of stay, complete remission and mortality) in AML patients hospitalized for initial induction therapy. A retrospective cohort study design was used. Records of 103 AML patients, hospitalized for initial induction chemotherapy were reviewed. Results of the study showed that 98% of the AML patients had at least one episode of hyperglycemia, with a prevalence rate of 33% over the entire induction inpatient hospitalization for this population. All patients noted with hyperglycemia also had hypoglycemia and thus, the prevalence rate of hypoglycemia alone could not be determined. Prevalence of the combination of hyperglycemia and hypoglycemia was 1.4 %. Although not statistically significant, a trend was noted for AML patients with hyperglycemia to experience more days with neutropenia, greater numbers of infection, sepsis, septicemia and death (mortality) than patients without hyperglycemia during induction treatment. Patients with the combination of hyperglycemia and hypoglycemia also experienced an increased risk of developing septicemia (p = .025) and sepsis (p =.057). Future studies with larger sample sizes are needed to confirm these findings.