How I treat acute myeloid leukemia

Blood ◽  
2010 ◽  
Vol 116 (17) ◽  
pp. 3147-3156 ◽  
Author(s):  
Jacob M. Rowe ◽  
Martin S. Tallman
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Allogeneic Transplantation ◽  
Malignant Cell ◽  
Current Approach ◽  
Molecular Abnormalities ◽  
The Past ◽  
Survival Pathways ◽  
Large Populations ◽  
Acute Myeloid

AbstractMore than one quarter of a million adults throughout the world are diagnosed annually with acute myeloid leukemia (AML). Despite considerable progress during the past 3 decades in the therapy of AML, two-thirds of young adults and 90% of older adults still die of their disease. The reported median age has increased over the past few decades, mostly because of a greater willingness of physicians to diagnose and treat older patients, and now is 72 years. The greatest challenge is in this age group. However, much improvement in therapy is needed for all adults with AML. Recent advances in allogeneic transplantation, a better understanding of prognostic factors, and development of targeted agents have only modestly improved overall outcome when large populations of patients are considered. Although an explosion in knowledge about the molecular pathogenesis of AML has outpaced treatment advances, such insights hold promise for the development of new therapies directed at specific molecular abnormalities that perturb malignant cell survival pathways. The current approach in 2010 to the management of this disease is presented through a discussion of illustrative cases.

scholarly journals Targeting multiple signaling pathways: the new approach to acute myeloid leukemia therapy

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Jenna L. Carter ◽  
Katie Hege ◽  
Jay Yang ◽  
Hasini A. Kalpage ◽  
Yongwei Su ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Acute Leukemia ◽  
Signaling Pathways ◽  
Myeloid Leukemia ◽  
Survival Rates ◽  
The Past ◽  
Survival Pathways ◽  
Therapeutic Development ◽  
Improvement In Survival ◽  
Acute Myeloid

AbstractAcute myeloid leukemia (AML) is the most common form of acute leukemia in adults and the second most common form of acute leukemia in children. Despite this, very little improvement in survival rates has been achieved over the past few decades. This is partially due to the heterogeneity of AML and the need for more targeted therapeutics than the traditional cytotoxic chemotherapies that have been a mainstay in therapy for the past 50 years. In the past 20 years, research has been diversifying the approach to treating AML by investigating molecular pathways uniquely relevant to AML cell proliferation and survival. Here we review the development of novel therapeutics in targeting apoptosis, receptor tyrosine kinase (RTK) signaling, hedgehog (HH) pathway, mitochondrial function, DNA repair, and c-Myc signaling. There has been an impressive effort into better understanding the diversity of AML cell characteristics and here we highlight important preclinical studies that have supported therapeutic development and continue to promote new ways to target AML cells. In addition, we describe clinical investigations that have led to FDA approval of new targeted AML therapies and ongoing clinical trials of novel therapies targeting AML survival pathways. We also describe the complexity of targeting leukemia stem cells (LSCs) as an approach to addressing relapse and remission in AML and targetable pathways that are unique to LSC survival. This comprehensive review details what we currently understand about the signaling pathways that support AML cell survival and the exceptional ways in which we disrupt them.

scholarly journals Human-level recognition of blast cells in acute myeloid leukemia with convolutional neural networks

2019 ◽  
Author(s):  
Christian Matek ◽  
Simone Schwarz ◽  
Karsten Spiekermann ◽  
Carsten Marr
Keyword(s):  
Acute Myeloid Leukemia ◽  
Blood Cells ◽  
Myeloid Leukemia ◽  
White Blood Cells ◽  
Cell Types ◽  
Hematologic Malignancies ◽  
Malignant Cell ◽  
Morphological Examination ◽  
Blast Cells ◽  
Acute Myeloid

AbstractReliable recognition of malignant white blood cells is a key step in the diagnosis of hematologic malignancies such as Acute Myeloid Leukemia. Microscopic morphological examination of blood cells is usually performed by trained human examiners, making the process tedious, time-consuming and hard to standardise.We compile an annotated image dataset of over 18,000 white blood cells, use it to train a convolutional neural network for leukocyte classification, and evaluate the network’s performance. The network classifies the most important cell types with high accuracy. It also allows us to decide two clinically relevant questions with human-level performance, namely (i) if a given cell has blast character, and (ii) if it belongs to the cell types normally present in non-pathological blood smears.Our approach holds the potential to be used as a classification aid for examining much larger numbers of cells in a smear than can usually be done by a human expert. This will allow clinicians to recognize malignant cell populations with lower prevalence at an earlier stage of the disease.

scholarly journals Outcomes of Older Patients with NPM1 Mutated and FLT3-ITD Negative Acute Myeloid Leukemia Receiving Allogeneic Transplantation

HemaSphere ◽  
2020 ◽  
Vol 4 (1) ◽  
pp. e326
Author(s):  
Madlen Jentzsch ◽  
Juliane Grimm ◽  
Marius Bill ◽  
Karoline Goldmann ◽  
Julia Schulz ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Allogeneic Transplantation ◽  
Acute Myeloid

scholarly journals MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia

Blood ◽  
2008 ◽  
Vol 111 (6) ◽  
pp. 3183-3189 ◽  
Author(s):  
Ramiro Garzon ◽  
Stefano Volinia ◽  
Chang-Gong Liu ◽  
Cecilia Fernandez-Cymering ◽  
Tiziana Palumbo ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Mirna Expression ◽  
Myeloid Leukemia ◽  
Cox Regression ◽  
Independent Set ◽  
Microarray Platform ◽  
Small Subset ◽  
Trisomy 8 ◽  
Molecular Abnormalities ◽  
Acute Myeloid

Abstract MicroRNAs (miRNAs) are small RNAs of 19 to 25 nucleotides that are negative regulators of gene expression. To determine whether miRNAs are associated with cytogenetic abnormalities and clinical features in acute myeloid leukemia (AML), we evaluated the miRNA expression of CD34+ cells and 122 untreated adult AML cases using a microarray platform. After background subtraction and normalization using a set of housekeeping genes, data were analyzed using Significance Analysis of Microarrays. An independent set of 60 untreated AML patients was used to validate the outcome signatures using real-time polymerase chain reaction. We identified several miRNAs differentially expressed between CD34+ normal cells and the AML samples. miRNA expression was also closely associated with selected cytogenetic and molecular abnormalities, such as t(11q23), isolated trisomy 8, and FLT3-ITD mutations. Furthermore, patients with high expression of miR-191 and miR-199a had significantly worse overall and event-free survival than AML patients with low expression (overall survival: miR-191, P = .03; and miR-199a, P = .001, Cox regression). In conclusion, miRNA expression in AML is closely associated with cytogenetics and FLT3-ITD mutations. A small subset of miRNAs is correlated with survival.

Monocytic Maturation Induced by FLT3 Inhibitor Therapy of Acute Myeloid Leukemia: Morphologic and Immunophenotypic Characteristics

2019 ◽  
Vol 51 (5) ◽  
pp. 478-483
Author(s):  
Cade D Arries ◽  
Sophia L Yohe
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Cell Population ◽  
Myeloid Leukemia ◽  
Inhibitor Therapy ◽  
Molecular Abnormalities ◽  
Flt3 Inhibitor ◽  
Flt3 Inhibitors ◽  
Acute Myeloid

Abstract Background FMS-like tyrosine kinase-3 (FLT3-ITD) mutations are some of the most common mutations in acute myeloid leukemia (AML), and patient outcomes have improved since the advent of tyrosine kinase inhibitors. First, granulocytic differentiation was described in FLT3-positive AML treated with FLT3 inhibitors, and more recently, monocytic differentiation was reported. Methods Two patients with myelomonocytic cells in their bone marrow were identified during routine follow-up after AML treatment that included FLT3 inhibitors. The bone marrow study was done as standard of care. Results Both patients had FLT3-ITD+ AML and showed an atypical maturing monocytic cell population and a decrease in the leukemic blast cell population after FLT3 inhibitor therapy. Concurrent genetic testing revealed persistent genetic abnormalities. Conclusions These cases illustrate monocytic maturation in FLT3+ AML after FLT3 inhibitor treatment. It is critical for pathologists and clinicians to be aware of the differentiation phenomenon, as these patients have persistent molecular abnormalities despite response to treatment and normalization of blast counts.

GAS6 Oncogene and Reverse MLLT3-KMT2A Duplications in an Infant with Acute Myeloid Leukemia and a Novel Complex Hyperdiploid Karyotype: Detailed High-Resolution Molecular Cytogenetic Studies

2017 ◽  
Vol 152 (1) ◽  
pp. 33-37
Author(s):  
Roberto R. Capela de Matos ◽  
Daniela R. Ney Garcia ◽  
Elaine Cifoni ◽  
Moneeb A.K. Othman ◽  
Mariana Tavares de Souza ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Resolution ◽  
Myeloid Leukemia ◽  
Molecular Cytogenetic ◽  
Severe Diarrhea ◽  
Molecular Abnormalities ◽  
Cytogenetic Studies ◽  
Novel Complex ◽  
Ploidy Changes ◽  
Acute Myeloid

Pediatric acute myeloid leukemia (AML) is a highly heterogeneous disease, presenting cytogenetic and molecular abnormalities which turned out to be critical prognostic factors. Ploidy changes as gain or loss of individual chromosomes are rare in AML, occurring only in about 1-2% of the affected children. Hyperdiploid karyotypes are exceedingly rare in infants less than 12 months of age. In this age group, structural rearrangements involving the KMT2A gene occur in about 58% of the cases. Among them, the translocation t(9;11)(p22;q23), KMT2A-MLLT3, is the most common abnormality accounting for approximately 22% of KMT2A rearrangements in infant AML cases. Here, we describe a 7- month-old girl with a history of fever and severe diarrhea, and a physical examination remarkable for pallor and hepatosplenomegaly. A novel complex hyperdiploid karyotype 53,XX,+X,+6,t(9;11)(p21.3;q23.3),+der(9)t(9;11)(p21.3;q23.3),dup(13)(q31q34),+14,+19,+21,+22 was characterized by high-resolution molecular cytogenetic approaches. Fluorescence in situ hybridization, multiplex-FISH, and multicolor chromosome banding were applied, revealing 2 reverse MLLT3-KMT2A fusions and a duplication of the GAS6 oncogene. Our work suggests that molecular cytogenetic studies are crucial for the planning of a proper strategy for risk therapy in AML infants with hyperdiploid karyotypes.

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