Genetic Abnormalities and Challenges in the Treatment of Acute Myeloid Leukemia

Abstract

Acute myeloid leukemia (AML) is a hematopoietic disorder in which there are too many immature blood-forming cells accumulating in the bone marrow and interfering with the production of normal blood cells. It has long been recognized that AML is a clinically heterogeneous disease characterized by a multitude of chromosomal abnormalities and gene mutations, which translate to marked differences in responses and survival following chemotherapy. The cytogenetic and molecular genetic aberrations associated with AML are not mutually exclusive and often coexist in the leukemic cells. AML is a disease of the elderly, with a mean age of diagnosis of 70 years. Adverse cytogenetic abnormalities increase with age, and within each cytogenetic group, prognosis with standard treatment worsens with age. In the past 20 years, there has been little improvement in chemotherapeutic regimens and hence the overall survival for patients with AML. A huge unmet need exists for efficacious targeted therapies for elderly patients that are less toxic than available chemotherapy regimens. The multitude of chromosomal and genetic abnormalities makes the treatment of AML a challenging prospect. A detailed understanding of the molecular changes associated with the chromosomal and genetic abnormalities in AML is likely to provide a rationale for therapy design and biomarker development. This review summarizes the variety of cytogenetic and genetic changes observed in AML and gives an overview of the clinical status of new drugs in development.

Enhancement of baicalin by hexamethylene bisacetamide on the induction of apoptosis contributes to simultaneous activation of the intrinsic and extrinsic apoptotic pathways in human leukemia cells

“…AML accounts for ~25% of all leukemias diagnosed in adults and its incidence is stably increasing (1). In the past two decades, there has been little improvement in chemotherapeutic regimens and hence the overall survival for patients with AML remains poor, with a 5-year survival rate of ~20% (2,3) and median survival times of only a few months for elderly patients (4). This is partly due to a higher prevalence of unfavorable cytogenetics and myelodysplasia, a higher incidence of MDR, and more frequent comorbidities that often render them unsuitable for intensive treatment (4,5).…”

Childhood Leukemias in Khyber Pakhtunkhwa and Afghan Children Visiting to Hayatabad Medical Complex Hospital

“…Acute Myeloid Leukemia (AML) is a diverse colonel hematological malignancy characterized by lack of differentiation and overgrowth of myeloid blasts lead to bone marrow failure. AML is further classified by French, American and British (FAB) into M0 to M7 subtypes [5]. Chronic myeloid leukemia (CML) is less common childhood leukemia, and rarely few cases of chronic Myelomonoctic leukemia (CMML) and juvenile chronic Myelomonocytic leukemia (JMML) were also reported in children [6,7].…”

Azacitidine for Treating Acute Myeloid Leukaemia with More Than 30 % Bone Marrow Blasts: An Evidence Review Group Perspective of a National Institute for Health and Care Excellence Single Technology Appraisal

“…AML progresses rapidly and may lead to fatal infections, bleeding or organ infiltration within months if left untreated [5]. Treatment with curative intent requires an aggressive chemotherapy regimen.…”

“…In AML, immature blood-forming cells accumulate in the bone marrow, blood, and organs, and interfere with the production of normal blood cells. AML can arise de novo, due to the progression of other diseases (e.g., myelodysplastic syndrome, MDS) or due to exposure to cytotoxic agents [5]. More than half (55%) of new cases of AML are diagnosed in people aged 70 and over [6].…”