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INTRODUCTION Acute myeloid leukemia (AML) is a neoplasm of the myeloid blood cells, which is characterized by unrestrained growth of white blood cells. The abnormal cells accumulate in the bone marrow where they interfere with the production of normal blood cells. AML is a relatively rare malignancy and accounts for only approximately 1% of cancers deaths in the US. However, the most common acute leukemia affecting adults and the incidence increases with age, which is why the incidence is expected to rise dramatically as the population ages. The symptoms of AML include fatigue, shortness of breath, easy bruising and bleeding, and increased risk of infection. All of these symptoms are the result of abnormal myeloid cells replacing normal bone marrow. This causes a decrease in the cells produced by the bone marrow including red blood cells, platelets, and normal white blood cells. The initial diagnosis of AML is usually made by an abnormal complete blood count. The most common finding is leukocytosis, increased white blood cells, although abnormal white cells are also seen. AML can also present with decreased platelets and red blood cells. Definitive diagnosis of AML requires a bone marrow aspirate biopsy to differentiate AML from other types of leukemia and to classify the subtype. According to the widely used WHO criteria, the diagnosis of AML is established by demonstrating more than 20% myeloblasts in the blood and/or bone marrow. There are several subtypes of AML with varying prognoses. Five-year survival varies from 15–70%, and relapse rate varies from 33-78%, depending on subtype. PROSNOSTIC INDICATORS The single most important prognostic factor in AML is the specific cytogenetic abnormality associated with the disease. Some abnormalities are associated with very good outcomes, such as the t(15:17) translocation, whereas others are associated with a poor prognosis and a high risk of relapse after treatment. Approximately 50% of AML patients have “normal” cytogenetics and these patients fall into an intermediate risk category. Other genetic factors also play into prognosis in AML. Internal tandem duplications in the Fms-like tyrosine kinase 3 (FLT3) are indicative of poor prognosis in AML. While the clinical significance of FLT3 remains unclear, it can be useful in determining the most effective treatment. TREATMENT AML is an aggressive acute leukemia that progresses quickly and is typically fatal within weeks or months if left untreated. Initial treatment of AML is two phase chemotherapy. The first phase is induction. In this phase, the goal of chemotherapy is a complete remission in which abnormal white cells become undetectable. The second phase is consolidation, which aims to completely eliminate undetectable, residual disease, thus curing the patient. Some patients may be eligible to receive a hematopoietic stem cell transplant to restore bone marrow function either after a relapse or if they have a specifically high risk subtype. FLT3 INHIBITORS AML remains one of the most difficult hematological malignancies to treat as it has a high rate of relapse after therapy and frequent poor outcomes. The high frequency of activating FLT3 mutations associated with poor prognosis in these patients has lead researchers to investigate potential FLT3 based therapies. High-throughput screening has identified a potential FLT3 tyrosine kinase inhibitor known as Quizartinib (AC220). Phase II clinical trials are currently underway to determine the efficacy of quizartinib in treatment of AML. Quizartinib is being tested as both a stand-alone treatment and in combination with other therapies for refractory AML. Interim analysis of the data from the trial has indicated favorable outcomes and development of the drug is likely to continue to phase III trials soon. SUMMARY Acute myeloid leukemia (AML) is a somewhat rare hematological malignancy with increasing incidence as the population in the US ages. There are several subtypes, which can be differentiated at diagnosis based on cytogenetics. Prognosis is highly dependent on the specific subtype identified. AML is an aggressive disease that is fatal within a few months if not treated. Even so, it remains very difficult to treat and prone to relapse. Activating mutations of the FLT3 tyrosine kinase have been associated with very poor prognosis in AML. For this reason, quizartinib, a FLT3 tyrosine kinase inhibitor is currently being investigated for treatment of AML. REFERENCES 1. Vardiman JW, Harris NL, Brunning RD (2002). “The World Health Organization (WHO) classification of the myeloid neoplasms”. Blood 100 (7): 2292–302. 2. Le Beau M, Albain K, Larson R, Vardiman J, Davis E, Blough R, Golomb H, Rowley J (1986). “Clinical and cytogenetic correlations in 63 patients with therapy-related myelodysplastic syndromes and acute nonlymphocytic leukemia: further evidence for characteristic abnormalities of chromosomes no. 5 and 7?. J Clin Oncol 4 (3): 325–45. 3. Taylor GM, Birch JM (1996). “The hereditary basis of human leukemia”. In Henderson ES, Lister TA, Greaves MF. Leukemia (6th ed.). Philadelphia: WB Saunders. p. 210. 4. Bishop J (1997). “The treatment of adult acute myeloid leukemia”. Semin Oncol 24 (1): 57–69. 5. Estey E (2001). “Prognostic factors in acute myelogenous leukemia”. Leukemia 15 (4): 670–2. 6. Schnittger S, Schoch C, Dugas M, Kern W, Staib P, Wuchter C, Löffler H, Sauerland C, Serve H, Büchner T, Haferlach T, Hiddemann W (2002). “Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual disease”. Blood 100 (1): 59–66. 7. Chao, Qi; Sprankle, Kelly G.; Grotzfeld, Robert M.; Lai, Andiliy G.; Carter, Todd A.; Velasco, Anne Marie; Gunawardane, Ruwanthi N.; Cramer, Merryl D.; Gardner, Michael F.; James, Joyce; Zarrinkar, Patrick P.; Patel, Hitesh K.; Bhagwat, Shripad S. (2009). “Identification of N-(5-tert-Butyl-isoxazol-3-yl)-N’-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea Dihydrochloride (AC220), a Uniquely Potent, Selective, and Efficacious FMS-Like Tyrosine Kinase-3 (FLT3) Inhibitor”. Journal of Medicinal Chemistry 52 (23): 7808–7816. 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