Acute promyelocytic leukemia causes: Difference between revisions
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**''DNMT3A'': ''[[DNA]] methyltransferase 3a'' (''DNMT3A'') is a gene that encodes an enzyme that methylates DNA. In general, ''DNMT3A'' mutations are rare in acute promyelocytic leukemia.<ref name="pmid24495159">{{cite journal| author=Greim H, Kaden DA, Larson RA, Palermo CM, Rice JM, Ross D et al.| title=The bone marrow niche, stem cells, and leukemia: impact of drugs, chemicals, and the environment. | journal=Ann N Y Acad Sci | year= 2014 | volume= 1310 | issue= | pages= 7-31 | pmid=24495159 | doi=10.1111/nyas.12362 | pmc=4002179 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24495159 }} </ref> | **''DNMT3A'': ''[[DNA]] methyltransferase 3a'' (''DNMT3A'') is a gene that encodes an enzyme that methylates DNA. In general, ''DNMT3A'' mutations are rare in acute promyelocytic leukemia.<ref name="pmid24495159">{{cite journal| author=Greim H, Kaden DA, Larson RA, Palermo CM, Rice JM, Ross D et al.| title=The bone marrow niche, stem cells, and leukemia: impact of drugs, chemicals, and the environment. | journal=Ann N Y Acad Sci | year= 2014 | volume= 1310 | issue= | pages= 7-31 | pmid=24495159 | doi=10.1111/nyas.12362 | pmc=4002179 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24495159 }} </ref> | ||
**''ASXL1'': ''Additional sex combs like 1'' (''ASXL1'') is a [[transcription]] [[Regulator gene|regulator]] and a modulator of [[histone]] [[methylation]]. [[Mutation|Mutations]] in this [[gene]] are associated with a very poor [[prognosis]] in [[acute myeloid leukemia]]. | **''ASXL1'': ''Additional sex combs like 1'' (''ASXL1'') is a [[transcription]] [[Regulator gene|regulator]] and a modulator of [[histone]] [[methylation]]. [[Mutation|Mutations]] in this [[gene]] are associated with a very poor [[prognosis]] in [[acute myeloid leukemia]]. | ||
**''EZH2'': ''Enhancer of zeste'' (''EZH2'') is a gene involved in the maintenance of transcription repression. It encodes a subunit of a histone methyltransferase.<ref name="pmid24495159">{{cite journal| author=Greim H, Kaden DA, Larson RA, Palermo CM, Rice JM, Ross D et al.| title=The bone marrow niche, stem cells, and leukemia: impact of drugs, chemicals, and the environment. | journal=Ann N Y Acad Sci | year= 2014 | volume= 1310 | issue= | pages= 7-31 | pmid=24495159 | doi=10.1111/nyas.12362 | pmc=4002179 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24495159 }} </ref> | **''EZH2'': ''Enhancer of zeste'' (''EZH2'') is a [[gene]] involved in the maintenance of [[Transcription (genetics)|transcription]] [[Repression of heat shock gene expression (ROSE) element|repression]]. It encodes a [[Protein subunit|subunit]] of a [[histone]] [[methyltransferase]].<ref name="pmid24495159">{{cite journal| author=Greim H, Kaden DA, Larson RA, Palermo CM, Rice JM, Ross D et al.| title=The bone marrow niche, stem cells, and leukemia: impact of drugs, chemicals, and the environment. | journal=Ann N Y Acad Sci | year= 2014 | volume= 1310 | issue= | pages= 7-31 | pmid=24495159 | doi=10.1111/nyas.12362 | pmc=4002179 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24495159 }} </ref> | ||
**''SRSF2'': ''Serine and arginine rich splicing factor 2'' (''SRSF2'') is a gene that encodes a splicosome component. Mutations in this gene are also involved in myelodysplastic syndrome. | **''SRSF2'': ''[[Serine]] and [[arginine]] rich splicing factor 2'' (''SRSF2'') is a [[gene]] that encodes a splicosome component. [[Mutation|Mutations]] in this [[gene]] are also involved in [[myelodysplastic syndrome]]. | ||
**''SF3B1'': ''Splicing factor 3b subunit 1'' (''SF3B1'') is a gene that encodes for a splicosome component. Mutations in this gene are also involved in myelodysplastic syndrome and presence of ringed sideroblasts. | **''SF3B1'': ''Splicing factor 3b subunit 1'' (''SF3B1'') is a gene that encodes for a splicosome component. Mutations in this gene are also involved in myelodysplastic syndrome and presence of ringed sideroblasts. | ||
**''IDH2'': ''Isocitrate dehydrogenase 2'' (''IDH2'') is a gene that encodes for an enzyme that results in the production of 2-hydroxyglutarate, which is an oncometabolite that results in a differentiation block.<ref name="pmid29346477">{{cite journal| author=Patel SA| title=Enasidenib-Induced Differentiation Syndrome in IDH2-Mutant Acute Myeloid Leukemia. | journal=JAMA Oncol | year= 2018 | volume= | issue= | pages= | pmid=29346477 | doi=10.1001/jamaoncol.2017.4724 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29346477 }} </ref> The differentiation block that arises from ''IDH2'' mutations is similar pathophysiologically to the differentiation block that occurs with the ''PML-RARA'' translocation.<ref name="pmid29346477">{{cite journal| author=Patel SA| title=Enasidenib-Induced Differentiation Syndrome in IDH2-Mutant Acute Myeloid Leukemia. | journal=JAMA Oncol | year= 2018 | volume= | issue= | pages= | pmid=29346477 | doi=10.1001/jamaoncol.2017.4724 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29346477 }} </ref> | **''IDH2'': ''Isocitrate dehydrogenase 2'' (''IDH2'') is a gene that encodes for an enzyme that results in the production of 2-hydroxyglutarate, which is an oncometabolite that results in a differentiation block.<ref name="pmid29346477">{{cite journal| author=Patel SA| title=Enasidenib-Induced Differentiation Syndrome in IDH2-Mutant Acute Myeloid Leukemia. | journal=JAMA Oncol | year= 2018 | volume= | issue= | pages= | pmid=29346477 | doi=10.1001/jamaoncol.2017.4724 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29346477 }} </ref> The differentiation block that arises from ''IDH2'' mutations is similar pathophysiologically to the differentiation block that occurs with the ''PML-RARA'' translocation.<ref name="pmid29346477">{{cite journal| author=Patel SA| title=Enasidenib-Induced Differentiation Syndrome in IDH2-Mutant Acute Myeloid Leukemia. | journal=JAMA Oncol | year= 2018 | volume= | issue= | pages= | pmid=29346477 | doi=10.1001/jamaoncol.2017.4724 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29346477 }} </ref> | ||
Revision as of 19:07, 11 January 2019
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Shyam Patel [2]
Overview
The cause of acute promyelocytic leukemia is sporadic rather than hereditary. It is caused by a reciprocal translocation between chromosomes 15 and 17, which creates a novel protein known as PML-RARA, leading to a differentiation block. In general, the causes of acute leukemia of myeloid origin include chemicals, radiation, cytotoxic chemotherapeutic agents, and specific mutations.
Acute promyelocytic leukemia causes
- Benzene: Benzene is a chemical liquid chemical with a sweet odor and is used in a variety of products, including heaters and other appliances. This chemical is a known cause of acute myeloid leukemia. In general, benzene exposure accounts for a very small fraction of acute promyelocytic leukemia, since most cases are sporadic.[1][2]
- Radiation: Ionizing radiation is known cause of acute leukemia of myeloid origin. Radiation inducing DNA damage, which can result in leukemia. In general, ionizing radiation accounts for a very small fraction of acute promyelocytic leukemia, since most cases are sporadic.[1]
- Alkylating agents: Chemotherapy agents that function via DNA alkylation are known to contribute to acute promyelocytic leukemia. Alkylating agents include nitrogen mustards (such as carmustine (BCNU) and lomustine (CCNU) and cyclophosphamide. Alkylating agents typically cause late-onset leukemia: the latency between the exposure to the alkylating agent and the diagnosis of leukemia is usually 5-7 years. There is frequently an antecedent myelodysplastic phase (a precursor state of acute leukemia).[3][4]
- Topoisomerase II inhibitors: Chemotherapy agents that function via inhibition of topoisomerase II are known to contribute to acute promyelocytic leukemia. Topoisomerase II inhibitors include anthracyclines, etoposide (VP-16), and topotecan. Topoisomerase II inhibitors typically cause early-onset leukemia: the latency between the exposure to the topoisomerase II inhibitor and the diagnosis of leukemia is usually 2-3 years. These are usually associated with the MLL rearrangement on chromosome 11q23.[5][6]
- Specific gene mutations: In rare cases, acute leukemia can arise in the setting of mutations. Most of these mutations are located in genes involved in epigenetic regulation. Such genes include TET2, DNMT3A, ASXL1, and EZH2. In addition to these, mutations in metabolic enzymes, such as IDH2 can contribute. These mutations are more common in acute myeloid leukemia compared to acute promyelocytic leukemia. Mutations can also occur in RNA splicing genes.[7][8][9]
- TET2: Ten eleven translocation 2 (TET2) is a gene that encodes an enzyme that catalyzes the conversion of methylcytosine to 5-hydroxymethylcytosine. Mutations in this gene result confer a worse prognosis for acute myeloid leukemia.[1]
- DNMT3A: DNA methyltransferase 3a (DNMT3A) is a gene that encodes an enzyme that methylates DNA. In general, DNMT3A mutations are rare in acute promyelocytic leukemia.[1]
- ASXL1: Additional sex combs like 1 (ASXL1) is a transcription regulator and a modulator of histone methylation. Mutations in this gene are associated with a very poor prognosis in acute myeloid leukemia.
- EZH2: Enhancer of zeste (EZH2) is a gene involved in the maintenance of transcription repression. It encodes a subunit of a histone methyltransferase.[1]
- SRSF2: Serine and arginine rich splicing factor 2 (SRSF2) is a gene that encodes a splicosome component. Mutations in this gene are also involved in myelodysplastic syndrome.
- SF3B1: Splicing factor 3b subunit 1 (SF3B1) is a gene that encodes for a splicosome component. Mutations in this gene are also involved in myelodysplastic syndrome and presence of ringed sideroblasts.
- IDH2: Isocitrate dehydrogenase 2 (IDH2) is a gene that encodes for an enzyme that results in the production of 2-hydroxyglutarate, which is an oncometabolite that results in a differentiation block.[10] The differentiation block that arises from IDH2 mutations is similar pathophysiologically to the differentiation block that occurs with the PML-RARA translocation.[10]
References
- ↑ 1.0 1.1 1.2 1.3 1.4 Greim H, Kaden DA, Larson RA, Palermo CM, Rice JM, Ross D; et al. (2014). "The bone marrow niche, stem cells, and leukemia: impact of drugs, chemicals, and the environment". Ann N Y Acad Sci. 1310: 7–31. doi:10.1111/nyas.12362. PMC 4002179. PMID 24495159.
- ↑ Zhang, L.; Samad, A.; Pombo-de-Oliveira, M.S.; Scelo, G.; Smith, M.T.; Feusner, J.; Wiemels, J.L.; Metayer, C. (2015). "Global characteristics of childhood acute promyelocytic leukemia". Blood Reviews. 29 (2): 101–125. doi:10.1016/j.blre.2014.09.013. ISSN 0268-960X.
- ↑ Casorelli, Ida; Bossa, Cecilia; Bignami, Margherita (2012). "DNA Damage and Repair in Human Cancer: Molecular Mechanisms and Contribution to Therapy-Related Leukemias". International Journal of Environmental Research and Public Health. 9 (8): 2636–2657. doi:10.3390/ijerph9082636. ISSN 1660-4601.
- ↑ Valentini, Caterina Giovanna; Fianchi, Luana; Voso, Maria Teresa; Caira, Morena; Leone, Giuseppe; Pagano, Livio (2011). "INCIDENCE OF ACUTE MYELOID LEUKEMIA AFTER BREAST CANCER". Mediterranean Journal of Hematology and Infectious Diseases. 3 (1): e2011069. doi:10.4084/mjhid.2011.069. ISSN 2035-3006.
- ↑ Felix, Carolyn A. (2001). "Leukemias related to treatment with DNA topoisomerase II inhibitors". Medical and Pediatric Oncology. 36 (5): 525–535. doi:10.1002/mpo.1125. ISSN 0098-1532.
- ↑ Pendleton, MaryJean; Lindsey, R. Hunter; Felix, Carolyn A.; Grimwade, David; Osheroff, Neil (2014). "Topoisomerase II and leukemia". Annals of the New York Academy of Sciences. 1310 (1): 98–110. doi:10.1111/nyas.12358. ISSN 0077-8923.
- ↑ Larsson, Connie A.; Cote, Gilbert; Quintás-Cardama, Alfonso (2013). "The Changing Mutational Landscape of Acute Myeloid Leukemia and Myelodysplastic Syndrome". Molecular Cancer Research. 11 (8): 815–827. doi:10.1158/1541-7786.MCR-12-0695. ISSN 1541-7786.
- ↑ DiNardo, C. D.; Cortes, J. E. (2016). "Mutations in AML: prognostic and therapeutic implications". Hematology. 2016 (1): 348–355. doi:10.1182/asheducation-2016.1.348. ISSN 1520-4391.
- ↑ Mazzarella, Luca; Riva, Laura; Luzi, Lucilla; Ronchini, Chiara; Pelicci, Pier Giuseppe (2014). "The Genomic and Epigenomic Landscapes of AML". Seminars in Hematology. 51 (4): 259–272. doi:10.1053/j.seminhematol.2014.08.007. ISSN 0037-1963.
- ↑ 10.0 10.1 Patel SA (2018). "Enasidenib-Induced Differentiation Syndrome in IDH2-Mutant Acute Myeloid Leukemia". JAMA Oncol. doi:10.1001/jamaoncol.2017.4724. PMID 29346477.