Acute Myeloid Leukemia (AML) Overview

AML is a blood cancer characterized by an infiltration of the bone marrow, blood, and other tissues by clonal, abnormal, and poorly differentiated cells of the hematopoietic system.1 Most cases of AML arise de novo, but some cases develop from antecedent hematopoietic disorders or prior treatment with cytotoxic therapy for other malignancies.2

Our understanding of the pathogenesis of AML has grown from recent advances in genomics, hematopoietic stem cell (HSC) biology, and studies using in vivo models.2 In normal hematopoiesis3:

  • Pluripotent stem cells are undifferentiated but are multipotential
  • Pluripotent HSCs differentiate into cells of the myeloid and lymphoid lineages
  • Myeloid progenitor cells differentiate into a variety of mature cells including red blood cells, platelets, and white blood cells
  • Lymphoid progenitor cells differentiate into B cells, T cells (lymphocytes), and NK cells
  • Normal feedback loops regulate cell production

Normal Hematopoiesis3

Genetic abnormalities in the DNA play an important role in the development of cancers such as AML.4 Though the precise events that lead to the development of a leukemic stem cell (LSC) are unclear, experimental evidence suggests that a stepwise accumulation of mutations in HSCs and progenitor cells leads to the fully transformed cells with impaired differentiation and unlimited self-renewal capacity4,5:

Abnormalities in the DNA That Lead to AML3-5

Acute myeloid leukemia (AML) is a clonal hematopoietic disorder that results from genetic alterations in normal hematopoietic stem cells. These alterations interrupt normal differentiation and/or cause excessive proliferation of abnormal immature leukemic cells known as blasts. As the disease progresses, blast cells build up in the bone marrow, blood, and organs and interfere with the production of normal blood cells. This can lead to fatal infection, bleeding, or organ infiltration. AML is generally lethal in the absence of treatment.6

In about half of patients, chromosomal abnormalities are found by cytogenetic analysis, which is used for classification and prognostic risk.6,7

References: 1. Döhner H, Weisdorf DJ, Bloomfield CD. Acute myeloid leukemia. N Engl J Med. 2015;373(12):1136-1152. 2. Grove CS, Vassiliou GS. Acute myeloid leukaemia: a paradigm for the clonal evolution of cancer? Dis Model Mech. 2014;7(8):941-951. 3. Kaushansky K. Hematopoietic stem cells, progenitors, and cytokines. In: Williams Hematology. 8th Ed. McGraw-Hill Companies. 2010. 4. Chan SM, Majeti R. Role of DNMT3A, TET2, and IDH1/2 mutations in pre-leukemic stem cells in acute myeloid leukemia. Int J Hematol. 2013;98(6):648-657. 5. De Kouchkovsky I, Abdul-Hay M. Acute myleoid leukemia: a comprehensive review and 2016 update. Blood Cancer J. 2016;6(7):e441.
6. Kumar CC. Genetic abnormalities and challenges in the treatment of acute myeloid leukemia. Genes Cancer. 2011;2(2):95-107. 7. Wan TS. Cancer cytogenetics: methodology revisited. Ann Lab Med. 2014;34(6):413-425.