Acute myeloid leukemia historical perspective

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shyam Patel [2]; Grammar Reviewer: Natalie Harpenau, B.S.[3]


In the 17th and 18th centuries, scientists first discovered and described blood cells, which are the malignant cells in acute myeloid leukemia. In the 19th century, the first case of acute leukemia was described. In the 20th century, chemotherapy was introduced for the treatment of acute leukemia. The 21st century witnessed advancements in the understanding of disease biology, and targeted therapies for acute myeloid leukemia were introduced to the market.

Historical Perspective

  • In 130-200 AD, Galen first used the term cancer. This included hematologic and solid malignancies.
  • In 1674, Van Leeuwenhoek was the first scientist to discover red blood cells.[1]
  • In 1749, Joseph Lieutaud, a French anatomist, described what he called the globuli albicantes, which later came to be known as white blood cells.
  • In 1749, after De Sanc described globules blancs du pus, it became known that pus and inflammation were related to blood.
  • In 1774, William Hewson gave a detailed description of the lymphatic system and lymphocytes.
  • In 1846, Dr. Henry Fuller, a physician at St George's Hospital in London, published the first case report of chronic granulocytic leukemia. This was the first recorded use of the microscope to diagnose leukemia in a patient. He noted that the time from the onset of ill health to death was 8 months. He labeled his diagnosis as "leucocythaemia".
  • In 1857, Nikolaus Friedreich documented the first case of acute leukemia.[2]
  • In 1877, Paul Ehrlich performed polychromatophilic stains to classify leukemia into myeloid or lymphoid.[2]
  • In 1878, Ernst Neumann described the bone marrow as the origin of leukemia.[2]
  • In 1882, A.C. Doyle reported on the efficacy of arsenic in acute promyelocytic leukemia.[3]
  • In 1889, Willhelm Ebstein described leukemia as a fast and fatal disease.[2]
  • In 1900, Otto Naegeli described the differences between blasts (blood cancer cells) of myeloid versus lymphoid origin.[2]
  • In 1914, Theodor Boveri described the role of chromosomal aberrations in the development of cancer. This later became very important to the classification of acute myeloid leukemia, which is largely based on chromosomal abnormalities.[2]
  • In 1973, cytarabine and anthracyclines were introduced as induction therapy for acute myeloid leukemia.
  • In 2000, gemtuzumab ozogamycin was approved by the Food and Drug Administration and was introduced to the market after phase II data showed a 26% response rate.[4]
  • In 2010, gemtuzumab ozogamycin was taken off the market after data showed concerns about the safety and efficacy of this medication in acute myeloid leukemia.[4]
  • In 2017, the European LeukemiaNet (ELN) classification system was devised to help risk stratify patients with acute myeloid leukemia.[5]
  • In 2017, there were multiple new drugs approved for acute myeloid leukemia after a 40-year period of stagnation. These medications included midostaurin, enasidenib, CPX-351, and gemtuzumab ozogamycin (re-approved in 2017 after its discontinuation in 2010).
  • In 2018, ivosidenib was approved by the Food and Drug Administration after a phase 1 dose-escalation and dose-expansion study showed an overall response rate of 40%.[6]


  1. Coller BS (2015). "Blood at 70: its roots in the history of hematology and its birth". Blood. 126 (24): 2548–60. doi:10.1182/blood-2015-09-659581. PMC 4671105. PMID 26631112.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 Lagunas-Rangel FA, Chávez-Valencia V, Gómez-Guijosa MÁ, Cortes-Penagos C (2017). "Acute Myeloid Leukemia-Genetic Alterations and Their Clinical Prognosis". Int J Hematol Oncol Stem Cell Res. 11 (4): 328–339. PMC 5767295. PMID 29340131.
  3. Falchi L, Verstovsek S, Ravandi-Kashani F, Kantarjian HM (2016). "The evolution of arsenic in the treatment of acute promyelocytic leukemia and other myeloid neoplasms: Moving toward an effective oral, outpatient therapy". Cancer. 122 (8): 1160–8. doi:10.1002/cncr.29852. PMC 5042140. PMID 26716387.
  4. 4.0 4.1 Cowan AJ, Laszlo GS, Estey EH, Walter RB (2013). "Antibody-based therapy of acute myeloid leukemia with gemtuzumab ozogamicin". Front Biosci (Landmark Ed). 18: 1311–34. PMC 3683663. PMID 23747885.
  5. Li Z, Herold T, He C, Valk PJ, Chen P, Jurinovic V; et al. (2013). "Identification of a 24-gene prognostic signature that improves the European LeukemiaNet risk classification of acute myeloid leukemia: an international collaborative study". J Clin Oncol. 31 (9): 1172–81. doi:10.1200/JCO.2012.44.3184. PMC 3595425. PMID 23382473.
  6. Popovici-Muller J, Lemieux RM, Artin E, Saunders JO, Salituro FG, Travins J; et al. (2018). "Discovery of AG-120 (Ivosidenib): A First-in-Class Mutant IDH1 Inhibitor for the Treatment of IDH1 Mutant Cancers". ACS Med Chem Lett. 9 (4): 300–305. doi:10.1021/acsmedchemlett.7b00421. PMC 5900343. PMID 29670690.


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