Acute Myeloid Leukaemia
Tariq I. Mughal in Precision Haematological Cancer Medicine, 2018
This chapter briefly reviews the complex genetic landscape and treatment of patients with acute myeloid leukaemia (AML). Therapy-related AML is recognized as a subgroup of the World Health Organization 2016 classification of AML, classified as a therapy-related myeloid neoplasm, which also includes therapy-related myelodysplastic syndromes. The conventional treatment plan for most patients consists of remission induction followed by a post-remission, or 'consolidation' therapy. There can be no doubt of the additional prognostic impact of the refinements to the complex genetic and epigenetic landscape of AML. This is additive to the initial framework for risk stratification of AML, based on clinical features, biologics and cytogenetics. Allogeneic stem cell transplantation from an HLA-matched sibling donor has been standard treatment for patients with poor-risk AML in first complete remission since the 1980s. A substantial amount of high-quality genetic data has been garnered on patients with AML improving our understanding of the biology and informed a better genomic classification and prognostication methods.
Aetiology of cancer
Ian Peate in Nursing & Health Survival Guide, 2014
A minority of cancers is known to be hereditary (inherited), for example, some breast cancers. When cancer occurs because of an inherited gene mutation risk increases: this is termed genetic susceptibility. Some viruses are known to be carcinogens, for example, the human papilloma virus is associated with cancer of the cervix. Several agents can cause cancer in the environment: these are called carcinogens. The most common cancer is lung cancer, but tobacco smoking can also be strongly associated with other types of cancer, for example: Smoking increases the risk of developing acute myeloid leukaemia (blood cancer) and cervical cancer. Occupational cancer can occur as a result of working environments that involve direct exposure to a carcinogen or exposure to a carcinogen produced as part of a work process. Women with the highest levels of oestrogen and associated hormones have over twice the average risk of breast and uterine cancer, and higher risks of ovarian cancer.
Leukemias
Pat Price, Karol Sikora in Treatment of Cancer, 2020
This chapter reviews the leukemias and highlights how the astonishing pace of advances in cancer biology and the breakthroughs in gene-sequencing methods and bioinformatics have ushered in a new era in precision medicine. Historically, leukemias are often considered as “acute” and “chronic”. Acute leukemias are typically of rapid onset, whereas chronic leukemias usually appear to have evolved slowly before diagnosis; neither term refers to the severity of the disease. Most patients with acute myeloid leukemia present with signs and symptoms arising from bone marrow failure and organ infiltration by leukemic cells. Post-remission therapy, also known as intensification or consolidation therapy is designed to eradicate residual leukemic cells. It comprises drugs similar to those used in remission induction or a combination of new drugs. Acute lymphoblastic leukemia is a clinically aggressive, though potentially curable, and genetically complex disorder comprised of multiple subtypes of B-cell precursor lineage or T-cell precursor lineage cells.
Emerging molecular predictive and prognostic factors in acute myeloid leukemia
Published in Leukemia & Lymphoma, 2018
Shannon R. McCurdy, Mark J. Levis
Recurrent cytogenetic abnormalities have provided the backbone for prognosticating acute myeloid leukemia and predicting response to consolidative therapies for decades. However, more than 45% of acute myeloid leukemia patients have normal cytogenetics on both karyotype and fluorescence in situ hybridization at diagnosis. Increasingly utilized next-generation sequencing has led to the discovery of numerous recurrent molecular mutations in acute myeloid leukemia, which can currently be identified in 97.3% of patients. Despite the prevalence of dozens of these recurrent lesions, only NMP1, CEBPA, KIT, FLT3-ITD, and TP53 have been incorporated into widely accepted risk-stratification schemas, such as the 2017 National Comprehensive Cancer Network guidelines. Here we review the most frequent molecular genetic abnormalities, their utility in predicting relapse and survival, and their function as markers of minimal residual disease. We also provide a summary of sixteen common recurrent molecular abnormalities about which sufficient data exists (Table 1).
Erythrophagocytosis by leukemic blasts in acute myeloid leukemia with a normal karyotype and no detectable mutations
Published in Baylor University Medical Center Proceedings, 2020
N. Grant Collins, Heather M. O’Connor, Kathryn G. Lindsey
The phagocytosis of erythrocytes by leukemic blasts is a rare finding in acute myeloid leukemia and has been reported most commonly in monocytic and megakaryocytic morphologies. In the reported cases, erythrophagocytosis by leukemic blasts has been associated with t(8;16). This translocation is associated with a poor outcome independent of erythrophagocytosis. There has only been one reported case of erythrophagocytosis by leukemic blasts occurring in a patient with a normal karyotype. We report a 62-year-old woman with acute myeloid leukemia with monocytic features and a normal karyotype noted to have erythrophagocytosis by leukemic blasts.
Small molecule inhibitors in acute myeloid leukemia: from the bench to the clinic
Published in Expert Review of Hematology, 2014
Muneera Al-Hussaini, John F DiPersio
Many patients with acute myeloid leukemia will eventually develop refractory or relapsed disease. In the absence of standard therapy for this population, there is currently an urgent unmet need for novel therapeutic agents. Targeted therapy with small molecule inhibitors represents a new therapeutic intervention that has been successful for the treatment of multiple tumors (e.g., gastrointestinal stromal tumors, chronic myelogenous leukemia). Hence, there has been great interest in generating selective small molecule inhibitors targeting critical pathways of proliferation and survival in acute myeloid leukemia. This review highlights a selective group of intriguing therapeutic agents and their presumed targets in both preclinical models and in early human clinical trials.