Acute Promyelocytic Leukemia Facts No. 26 in a series providing the latest information for patients, caregivers and healthcare professionals Highlights About AML y Acute promyelocytic leukemia (APL) is a unique Leukemia is a cancer of the marrow and blood. subtype of acute myeloid leukemia (AML). The four major types of leukemia are acute myeloid APL cells have a very specific abnormality that leukemia (AML), chronic myeloid leukemia (CML), involves chromosomes 15 and 17, leading to the acute lymphoblastic leukemia (ALL) and chronic formation of an abnormal fusion gene called lymphocytic leukemia (CLL). Each of the main types PML/RARα. This mutated gene causes many of of leukemia is further classified into subtypes. Acute the features of the disease. promyelocytic leukemia (APL) is a unique subtype of AML (approximately 600-800 new cases each year y Promyelocytes are immature white blood in the US). cells. In APL, these cells are overproduced and accumulate in the bone marrow. Signs, In myeloid leukemia, a cancerous change begins in symptoms and complications of APL result from the bone marrow, in a stem cell that normally would the overproduction of promyelocytes and the develop into a blood cell—a red blood cell, some type underproduction of healthy blood cells. of white blood cell or a platelet. y Treatment with a drug called all-trans retinoic Acute promyelocytic leukemia (APL) gets its name acid (ATRA) targets chromosomal abnormality. from immature white blood cells called promyelocytes Arsenic trioxide (ATO) as a single agent has that accumulate in the marrow and crowd out other also proven successful in APL treatment. healthy cells. These cells are myeloblasts that have The combination of ATRA and ATO has been stopped maturing. (Healthy myeloblasts turn into FDA-approved for the treatment of adults with myelocytes and eventually become mature white newly diagnosed low-risk disease characterized blood cells called granulocytes: neutrophils, basophils, by the presence of the t(15;17) translocation and eosinophils). or PML/RARα gene expression. Other drug therapies that have increased remission APL cells have a specific chromosome abnormality and cure rates include anthracyclines and that involves a translocation of chromosome 15 and gemtuzumab ozogamicin (GO). chromosome 17, abbreviated as t(15;17), which creates an abnormal fusion gene called PML/RARα. This y Because of advances in diagnosis and treatment abnormality is present in about 95 percent of patients of this disease, APL is now considered the most diagnosed with APL. curable form of adult leukemia. Cure rates of 90 percent have been reported from centers The World Health Organization (WHO) classification specializing in APL treatment. is the main system used to classify AML into subtypes. The WHO developed this system to include chromosomal abnormalities and genetic mutations, which are known to affect prognosis (the likely outcome of the disease). These genetic factors help provide both doctor and patient with more reliable information about the patient’s prognosis and also help predict the patient’s response to treatment. Information about a person’s AML subtype helps the doctor recommend a specific treatment plan. The WHO classification is usually revised every eight years. The revised 2016 classification incorporates FACT SHEET Acute Promyelocytic Leukemia Facts new scientific and clinical information (see Table 1, Cancer Institute (NCI) SEER (Surveillance, Epidemiology, below). For the full WHO AML classification, and End Results Program) registry, for the period from please visit www.LLS.org/booklets to see the free 2013 to 2017, the age-adjusted annual incidence of booklet Acute Myeloid Leukemia. newly diagnosed cases was 0.34 per 100,000 persons— about 1 case per 294,000 persons. During that period, Table 1. World Health Organization AML Classification the median age of APL diagnosis was 51 years. The medial age of AML diagnosis is 68 years. Hispanics Acute Myeloid Leukemia (AML) and Related Neoplasms have the highest incidence rate of APL, while Asian and AML with Recurrent Genetic Inversion and/or Pacific Islanders have the lowest rate. Gene Abnormalities Translocation With current treatment, APL has become one of the most AML with t(8;21)(q22;q22.1)1 RUNX1-RUNX1T1 curable types of acute leukemia. People with APL who inv(16)(p13.1q22) or AML with CBFB-MYH11 receive treatment often have a normal or near-normal t(16;16)(p13.1;q22) quality of life. Acute promyelocytic t(15:17) PML-RAR leukemia (APL) α Please visit www.LLS.org/booklets to see the free LLS AML with t(9;11)(p21.3;q23.3) MLLT3-KMT2A booklet Understanding Genetics. AML with t(6;9)(p23;q34.1) DEK-NUP214 inv(3)(q21.3q26.2) or GATA2, AML with Signs and Symptoms t(3;3)(q21.3;q26.2) MECOM(EV11) It is common for people with APL to feel a loss of well- AML (megakaryoblastic) with t(1;22)(p13.3;q13.3) RBM15-MKL1 being because of the underproduction of normal blood AML with N/A mutated NPM1 cells as well as with the accumulation of leukemic cells Biallelic mutations AML with N/A in the bone marrow. of CEBPA Source: World Health Organization (WHO) classification. WHO categorizes AML Common signs and symptoms of APL include into groups based on recent discoveries in cytogenetic and clinical features of AML. Abbreviations: t, a translocation between chromosomes; inv, an inversion in a chromosome; q, the long arm of a chromosome (the lower half); p, the short arm y Pale complexion, caused by anemia of a chromosome (the upper half). y Signs of bleeding caused by a very low platelet count, including Treatment for APL differs from all other AML treatments. Because of advances in diagnosis and treatment, {{Black-and-blue marks or bruises occurring for no APL has been transformed from the most fatal to the reason or because of a minor injury most curable form of acute leukemia in adults. {{The appearance of pinhead-sized red spots This Fact Sheet provides current information about on the skin, called “petechiae” diagnosis, treatment, and new treatments being {{Prolonged bleeding from minor cuts investigated in clinical trials, along with support resources. y Fatigue Causes and Incidence y Mild fever Most APL cells have a specific chromosome abnormality y Swollen gums involving a balanced translocation (swapping) between y Frequent minor infections chromosomes 15 and 17 t(15;17), resulting in the y Loss of appetite abnormal fusion gene PML/RARα. This abnormality is a distinguishing feature of APL that causes the symptoms y Weight loss of the disease; it is also a key target of treatment. y Discomfort in bones or joints Among adults over age 20, APL represents y Enlarged spleen and liver approximately 7 percent of AML cases. There are approximately 1,100 new cases of APL each year in y Neurologic symptoms such as headache, confusion the United States. According to data from the National and visual changes (associated with APL that involves the central nervous system [CNS]) 2 Acute Promyelocytic Leukemia Facts Bleeding. A low platelet count and low amounts of clotting from the overproduction of promyelocytes and the factors predispose patients to bleeding. In addition, underproduction of healthy blood cells. patients with high white blood cell (WBC) counts at Doctors use the results of blood and bone marrow tests diagnosis are at increased risk for bleeding. Bleeding in to identify abnormal APL cells. A prompt diagnosis of APL the brain or lungs is serious and can be fatal. This kind of is vital because appropriate treatment must be started serious bleeding is usually preceded by minor bleeding, immediately in order to avoid the serious and potentially such as nosebleeds, blood in the urine, or bruises. life-threatening complications (especially bleeding in the Infection. Severe infection may be present at the time brain or lungs) associated with the disease. of diagnosis for some patients, due to low white blood Coagulation Tests. When APL is suspected, doctors cell counts. Infection may become more common may order “coagulation status” tests along with other and often more serious during treatment, when the laboratory tests and imaging scans, to help assess the bone marrow is completely suppressed. clotting status of the patient’s blood. Coagulation refers to the blood’s ability to form clots when necessary. This Diagnosis process is impaired in APL patients because patients When a patient is suspected of having leukemia, have fewer platelets and clotting factors in the blood. obtaining an accurate diagnosis of the type of leukemia Coagulation disorders can lead to heavy and prolonged is important. The exact diagnosis helps the doctor bleeding after an injury. Coagulation tests help prevent estimate how the disease will progress and determine or diagnose serious conditions such as deep-vein the appropriate course of treatment. Some of the tests thrombosis, pulmonary embolism and strokes. See the used for making a diagnosis may also be repeated Glossary on page 9 for more information on these terms. during and after therapy to measure the effects of Please visit www.LLS.org/booklets to see the free LLS treatment. booklet Understanding Lab and Imaging Tests. Blood and Bone Marrow Tests. A change in the number and appearance of blood cells helps the doctor make an Treatment Planning accurate diagnosis. APL cells may look similar to normal Treatment decisions are based on the patient’s age, immature white cells. However, their development is general health and APL risk classification. incomplete. APL is classified into the two following categories Blood samples are generally taken from a vein in the of risk, based on the patient’s white blood cell count patient’s arm. Samples of marrow cells are obtained at diagnosis: by bone marrow aspiration and biopsy.