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| {{SK}} Acute progranulocytic leukemia; APL; AML with t(15;17)(q22;q12); PML-RARA and variants; FAB subtype M3; M3 variant | | {{SK}} Acute progranulocytic leukemia; APL; AML with t(15;17)(q22;q12); PML-RARA and variants; FAB subtype M3; M3 variant |
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| ==Overview== | | ==[[Acute promyelocytic leukemia overview|Overview]]== |
| '''Acute promyelocytic leukemia''' is a subtype of [[acute myelogenous leukemia]] (AML), a [[cancer]] of the [[blood]] and [[bone marrow]].
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| In APL, there is an abnormal accumulation of immature [[granulocytes]] called promyelocytes. The disease is characterized by a [[chromosomal translocation]] involving the [[retinoic acid receptor]] alpha (''RARα'' or ''RARA'') gene and is unique from other forms of AML in its responsiveness to [[ATRA|all ''trans'' retinoic acid]] (ATRA) therapy.
| | ==[[Acute promyelocytic leukemia historical perspective|Historical Perspective]]== |
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| ==Signs and symptoms== | | ==[[Acute promyelocytic leukemia classification|Classification]]== |
| Signs and symptoms of acute promyelocytic leukemia are similar to other forms of AML. Symptoms include [[fever]], [[fatigue (physical)|fatigue]], [[weight loss]] or loss of appetite, shortness of breath with exertion, [[anemia]], easy bruising or bleeding, [[petechiae]] (flat, pin-head sized spots under the skin caused by bleeding), bone pain and joint pain and persistent or frequent infections.[8]
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| The accumulation of promyelocytes in the bone marrow results in a reduction in the production of normal [[red blood cell]]s and [[platelet]]s resulting in [[anemia]] and [[thrombocytopenia]]. Either [[leukopenia]] (low white cell count) or [[leukocytosis]] (high white cell count) may be observed in the peripheral blood.
| | ==[[Acute promyelocytic leukemia pathophysiology|Pathophysiology]]== |
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| Symptoms include:
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| *Fatigue, weakness, shortness of breath (from anemia)
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| *Easy bruising and bleeding (from thrombocytopenia and [[coagulopathy]])
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| *Fever and infection (from lack of normal white blood cells)
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| In addition, acute promyelocytic leukemia is frequently associated with bleeding caused by [[disseminated intravascular coagulation]] (DIC).
| | ==[[Acute promyelocytic leukemia differential diagnosis|Differentiating Acute promyelocytic leukemia from Other Diseases]]== |
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| ==Epidemiology== | | ==[[Acute promyelocytic leukemia epidemiology and demographics|Epidemiology and Demographics]]== |
| Acute promyelocytic leukemia represents 5-8% of AML in adults. The median age is approximately 40 years, which is considerably younger than the other subtypes of AML (70 years). The incidence is increased in patients originated in Latin American countries.(Douer ''et al.'')
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| ==Pathophysiology== | | ==[[Acute promyelocytic leukemia risk factors|Risk Factors]]== |
| Acute promyelocytic leukemia is characterized by chromosomal translocation involving the retinoic acid receptor-alpha gene on chromosome 17 (''RARα''). In 95% of cases of APL, retinoic acid receptor-alpha (''RARα'') gene on chromosome 17 is involved in a reciprocal translocation with the promyelocytic leukemia gene (''PML'') on chromosome 15, a translocation denoted as t(15;17)(q22;q12). | |
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| Four other gene rearrangements have been described in APL fusing ''RARα'' to promyelocytic leukemia zinc finger (''PLZF''), nucleophosmin (''NPM''), nuclear matrix associated (''NUMA''), or signal transducer and activator of transcription 5b (''STAT5B'') genes.
| | ==[[Acute promyelocytic leukemia natural history|Natural History, Complications and Prognosis]]== |
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| The resultant fusion proteins disrupt the function of RARα which blocks the normal maturation of granulocytes. Although the chromosomal translocation involving ''RARα'' is believed to be the initiating event, additional mutations are required for the development of leukemia.
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| ==Diagnosis== | | ==Diagnosis== |
| Acute promyelocytic leukemia can be distinguished from other types of AML based on morphologic examination of a [[bone marrow biopsy]] or aspirate. Definitive diagnosis requires testing for the ''RARα'' fusion gene. This may be done by [[polymerase chain reaction]] (PCR), [[fluorescent in situ hybridization]] (FISH), or conventional [[cytogenetics]] of peripheral blood or bone marrow. | | [[Acute promyelocytic leukemia history and symptoms|History and Symptoms]] | [[Acute promyelocytic leukemia physical examination|Physical Examination]] | [[Acute promyelocytic leukemia laboratory tests|Laboratory Findings]] | [[Acute promyelocytic leukemia chest x ray|Chest X Ray]] | [[Acute promyelocytic leukemia CT|CT]] | [[Acute promyelocytic leukemia other diagnostic studies|Other Diagnostic Studies]] |
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| Monitoring for relapse using PCR tests for ''RARα'' allows early re-treatment which is successful in many instances.
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| ==Treatment== | | ==Treatment== |
| APL is unique among the leukemias distinguished by its sensitivity to [[all-trans retinoic acid|all-''trans'' retinoic acid]] (ATRA), a derivative of [[vitamin A]]. Treatment with ATRA causes differentiation of the immature leukemic promyelocytes into mature granulocytes. ATRA is typically combined with [[anthracycline]] based chemotherapy resulting in a clinical remission in approximately 90% of patients.
| | [[Acute promyelocytic leukemia medical therapy#Overview|Medical Therapy Overview]] | [[Acute promyelocytic leukemia medical therapy#Chemotherapy|Chemotherapy]] | [[Acute promyelocytic leukemia medical therapy#Relapsed AML|Relapsed AML]] | [[Acute promyelocytic leukemia medical therapy#Supportive Therapy|Supportive Therapy]] |
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| ATRA therapy is associated with the unique side effect of [[retinoic acid syndrome]]. This is associated with the development of dyspnea, fever, weight gain, peripheral edema and is treated with [[dexamethasone]]. The etiology of retinoic acid syndrome has been attributed to capillary leak syndrome from cytokine release from the differentiating promyelocytes.
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| Treatment options for patients with relapsed disease include [[arsenic trioxide]] and [[bone marrow transplant|allogeneic stem cell transplant]].
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| ==References== | | ==Case Studies== |
| * Kumar, Vinay, Abul Abbas, and Nelson Fausto. ''Robbins and Cotran Pathologic Basis of Disease'', 7th ed. (2004). ISBN 81-8147-528-3
| | [[Acute promyelocytic leukemia case study one|Case #1]] |
| * Sacher, Ronald A. and Richard A. McPherson. ''Wildman's Clinical Interpretation of Laboratory Tests'', 11th ed. (2000). ISBN 0-8036-0270-7
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| * Dan Douer, et al. ''British Journal of Haematology'', vol. 122, pp. 563, Aug. 2003
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| * Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide, N Engl J Med. 1998 Nov 5;339(19):1341-8.
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| {{Hematological malignancy histology}} | | {{Hematological malignancy histology}} |