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==Acute promyelocytic leukemia causes== | ==Acute promyelocytic leukemia causes== | ||
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.<ref name="pmid29541170">{{cite journal| author=Chen C, Huang X, Wang K, Chen K, Gao D, Qian S| title=Early mortality in acute promyelocytic leukemia: Potential predictors. | journal=Oncol Lett | year= 2018 | volume= 15 | issue= 4 | pages= 4061-4069 | pmid=29541170 | doi=10.3892/ol.2018.7854 | pmc=5835847 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29541170 }} </ref> In general, the causes of acute leukemia of myeloid origin include chemicals, radiation, and | 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.<ref name="pmid29541170">{{cite journal| author=Chen C, Huang X, Wang K, Chen K, Gao D, Qian S| title=Early mortality in acute promyelocytic leukemia: Potential predictors. | journal=Oncol Lett | year= 2018 | volume= 15 | issue= 4 | pages= 4061-4069 | pmid=29541170 | doi=10.3892/ol.2018.7854 | pmc=5835847 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29541170 }} </ref> In general, the causes of acute leukemia of myeloid origin include chemicals, radiation, and epigenetic mutations. | ||
*'''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]].<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> In general, benzene exposure accounts for a very small fraction of acute promyelocytic leukemia, since most cases are sporadic. | *'''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]].<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> In general, benzene exposure accounts for a very small fraction of acute promyelocytic leukemia, since most cases are sporadic. | ||
*'''Radiation''': Ionizing radiation is known cause of acute [[leukemia]] of myeloid origin. In general, ionizing radiation accounts for a very small fraction of acute promyelocytic leukemia, since most cases are sporadic. | *'''Radiation''': Ionizing radiation is known cause of acute [[leukemia]] of myeloid origin. Radiation inducing DNA damage, which can result in 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> In general, ionizing radiation accounts for a very small fraction of acute promyelocytic leukemia, since most cases are sporadic. | ||
*'''Epigenetic mutations''': In some cases, acute [[leukemia]] can arise in the setting of epigenetic 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]]. | |||
**''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]].<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 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.<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> | |||
==References== | ==References== | ||
Revision as of 01:02, 21 May 2018
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Shyam Patel [2]
Acute promyelocytic leukemia causes
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.[1] In general, the causes of acute leukemia of myeloid origin include chemicals, radiation, and epigenetic mutations.
- 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.[2] In general, benzene exposure accounts for a very small fraction of acute promyelocytic leukemia, since most cases are sporadic.
- Radiation: Ionizing radiation is known cause of acute leukemia of myeloid origin. Radiation inducing DNA damage, which can result in leukemia.[2] In general, ionizing radiation accounts for a very small fraction of acute promyelocytic leukemia, since most cases are sporadic.
- Epigenetic mutations: In some cases, acute leukemia can arise in the setting of epigenetic 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.
- 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.[2]
- 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.[2]
- 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.[2]
References
- ↑ Chen C, Huang X, Wang K, Chen K, Gao D, Qian S (2018). "Early mortality in acute promyelocytic leukemia: Potential predictors". Oncol Lett. 15 (4): 4061–4069. doi:10.3892/ol.2018.7854. PMC 5835847. PMID 29541170.
- ↑ 2.0 2.1 2.2 2.3 2.4 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.