Editing Leukemia (section)

==Causes==

Studies in 2009 and 2010 have shown a positive correlation between exposure to [[formaldehyde]] and the development of leukemia, particularly [[myeloid leukemia]].<ref>{{cite journal
| last1=Zhang
| first1=Luoping
| last2=Steinmaus
| first2=Craig
| last3=Eastmond
| first3=Eastmond
| last4=Xin
| first4=Xin
| last5=Smith
| first5=Smith
| title=Formaldehyde exposure and leukemia: A new meta-analysis and potential mechanisms
| url=http://ehs.sph.berkeley.edu/krsmith/CRA/cancer/ZhangL_2008.pdf
| date=March–June 2009
| volume=681
| pages=150–168
| pmid=18674636
| doi=10.1016/j.mrrev.2008.07.002
| access-date=2013-05-22
| journal=Mutation Research/Reviews in Mutation Research
| issue=2–3
| archive-url=https://web.archive.org/web/20140327073359/http://ehs.sph.berkeley.edu/krsmith/CRA/cancer/ZhangL_2008.pdf
| archive-date=2014-03-27
| url-status=dead
}}</ref><ref>{{cite journal
| doi=10.1002/em.20534
| pmid=19790261
| title=Formaldehyde and Leukemia: Epidemiology, Potential Mechanisms, and Implications for Risk Assessment
| year=2010
| volume=51
| issue=3
| pages=181–191
| journal=Environmental and Molecular Mutagenesis| pmc=2839060
| last1=Zhang
| first1=Luoping
| last2=Freeman
| first2=Laura E. Beane
| last3=Nakamura
| first3=Jun
| last4=Hecht
| first4=Stephen S.
| last5=Vandenberg
| first5=John J.
| last6=Smith
| first6=Martyn T.
| last7=Sonawane
| first7=Babasaheb R.
| bibcode=2010EnvMM..51..181Z
}}</ref> The different leukemias likely have different causes.<ref>{{cite book | veditors = Novak EM, Rego EM | title = Physiopathogenesis of Hematological Cancer | publisher = Bentham Science Publishers | date = 2012 | isbn = 978-1-60805-259-2 }}</ref>

Leukemia, like other cancers, results from [[somatic mutation|mutations]] in the [[DNA]]. Certain mutations can trigger leukemia by activating [[oncogene]]s or deactivating [[tumor suppressor gene]]s, and thereby disrupting the regulation of cell death, differentiation or division. These mutations may occur spontaneously or as a result of exposure to [[ionizing radiation|radiation]] or [[carcinogen]]ic substances.<ref>{{cite journal | vauthors = Radivoyevitch T, Sachs RK, Gale RP, Molenaar RJ, Brenner DJ, Hill BT, Kalaycio ME, Carraway HE, Mukherjee S, Sekeres MA, Maciejewski JP | title = Defining AML and MDS second cancer risk dynamics after diagnoses of first cancers treated or not with radiation | journal = Leukemia | volume = 30 | issue = 2 | pages = 285–294 | date = February 2016 | pmid = 26460209 | doi = 10.1038/leu.2015.258 | s2cid = 22100511 }}</ref>

Among adults, the known causes are natural and artificial [[ionizing radiation]] and petrochemicals, notably [[benzene]] and alkylating [[chemotherapy]] agents for previous malignancies.<ref name="isbn1-55009-111-5">{{cite book| vauthors = Wiernik PH |title=Adult leukemias|publisher=B. C. Decker|location=New York|year=2001|pages=3–15|isbn=978-1-55009-111-3}}</ref><ref name="isbn1-893441-36-9">{{cite book | vauthors = Robinette MS, Cotter S, Van de Water D |title=Quick Look Series in Veterinary Medicine: Hematology|publisher=Teton NewMedia|year=2001|page=105|isbn=978-1-893441-36-1}}</ref><ref name="isbn0-8247-0170-4">{{cite book| vauthors = Stass SA, Schumacher HR, Rock WR |title=Handbook of hematologic pathology|url=https://archive.org/details/handbookhematolo00schu |url-access=limited |publisher=Marcel Dekker|location=New York, N.Y|year=2000|pages=[https://archive.org/details/handbookhematolo00schu/page/n208 193]–194|isbn=978-0-8247-0170-3}}</ref> Use of [[tobacco]] is associated with a small increase in the risk of developing [[acute myeloid leukemia]] in adults.<ref name="isbn1-55009-111-5" /> Cohort and case-control studies have linked exposure to some [[petrochemicals]] and [[hair dye]]s to the development of some forms of leukemia. Diet has very limited or no effect, although eating more vegetables may confer a small protective benefit.<ref name="pmid12163333">{{cite journal | vauthors = Ross JA, Kasum CM, Davies SM, Jacobs DR, Folsom AR, Potter JD | title = Diet and risk of leukemia in the Iowa Women's Health Study | journal = Cancer Epidemiology, Biomarkers & Prevention | volume = 11 | issue = 8 | pages = 777–781 | date = August 2002 | pmid = 12163333 | url = http://cebp.aacrjournals.org/content/11/8/777.long | url-status = live | archive-url = https://web.archive.org/web/20170910174529/http://cebp.aacrjournals.org/content/11/8/777.long | archive-date = 10 September 2017 }}</ref>

Viruses have also been linked to some forms of leukemia.  For example, [[human T-lymphotropic virus]] (HTLV-1) causes [[adult T-cell leukemia]].<ref>{{cite book| vauthors = Leonard B |title=Leukemia: A Research Report|year=1998|publisher=DIANE Publishing|isbn=978-0-7881-7189-5|page=[https://books.google.com/books?id=VfFCVvX9btYC&pg=PA7 7]|url=https://books.google.com/books?id=VfFCVvX9btYC&q=leukemia}}</ref>

A few cases of [[maternal-fetal transmission]] (a baby acquires leukemia because its mother had leukemia during the pregnancy) have been reported.<ref name="isbn1-55009-111-5" /> Children born to mothers who use [[fertility medication|fertility drugs]] to induce ovulation are more than twice as likely to develop leukemia during their childhoods than other children.<ref name="Rudant2012">{{cite journal | vauthors = Rudant J, Amigou A, Orsi L, Althaus T, Leverger G, Baruchel A, Bertrand Y, Nelken B, Plat G, Michel G, Sirvent N, Chastagner P, Ducassou S, Rialland X, Hémon D, Clavel J | title = Fertility treatments, congenital malformations, fetal loss, and childhood acute leukemia: the ESCALE study (SFCE) | journal = Pediatric Blood & Cancer | volume = 60 | issue = 2 | pages = 301–8 | date = February 2013 | pmid = 22610722 | doi = 10.1002/pbc.24192 | s2cid = 26010916 }}</ref>

In a recent systematic review and meta-analysis of any type of leukemia in neonates using [[Light therapy|phototherapy]], typically to treat [[neonatal jaundice]], a statistically significant association was detected between using phototherapy and myeloid leukemia. However, it is still questionable whether phototherapy is genuinely the cause of cancer or simply a result of the same underlying factors that gave rise to cancer.<ref>{{cite journal |vauthors=Abdellatif M, Tawfik GM, Makram AM, Abdelsattar MK, Dobs M, Papadopoulos DN, Hoang-Trong BL, Mostafa EM, Duong PD, Huy NT |title=Association between neonatal phototherapy and future cancer: an updated systematic review and meta-analysis |journal=Eur J Pediatr |volume=182 |issue=1 |pages=329–341 |date=January 2023 |pmid=36352244 |doi=10.1007/s00431-022-04675-6 }}</ref>

===Radiation===
Large doses of [[Strontium-90|Sr-90]] (called a [[bone seeker|bone seeking]] radioisotope) from [[nuclear reactor]] accidents, increases the risk of [[Osteosarcoma|bone cancer]] and leukemia in animals and is presumed to do so in people.<ref>{{cite web |title=Backgrounder on Radiation Protection and the "Tooth Fairy" Issue |url = https://www.nrc.gov/reading-rm/doc-collections/fact-sheets/tooth-fairy.html | archive-url = https://web.archive.org/web/20170720060330/https://www.nrc.gov/reading-rm/doc-collections/fact-sheets/tooth-fairy.html | archive-date = 20 July 2017 | publisher = U.S. Nuclear Regulatory Commission | date = December 2004 }}</ref>

===Genetic conditions===
Some people have a genetic predisposition towards developing leukemia. This predisposition is demonstrated by family histories and [[Twin study|twin studies]].<ref name="isbn1-55009-111-5" /> The affected people may have a single gene or multiple genes in common. In some cases, families tend to develop the same kinds of leukemia as other members; in other families, affected people may develop different forms of [[hematological malignancies|leukemia or related blood cancers]].<ref name="isbn1-55009-111-5" />

In addition to these genetic issues, people with chromosomal abnormalities or certain other genetic conditions have a greater risk of leukemia.<ref name="isbn1-893441-36-9" /> For example, people with [[Down syndrome]] have a significantly increased risk of developing forms of acute leukemia (especially [[acute myeloid leukemia]]), and [[Fanconi anemia]] is a risk factor for developing acute myeloid leukemia.<ref name="isbn1-55009-111-5" /> Mutation in [[SPRED1 gene]] has been associated with a predisposition to childhood leukemia.<ref>{{cite journal | vauthors = Pasmant E, Ballerini P, Lapillonne H, Perot C, Vidaud D, Leverger G, Landman-Parker J | title = SPRED1 disorder and predisposition to leukemia in children | journal = Blood | volume = 114 | issue = 5 | pages = 1131 | date = July 2009 | pmid = 19643996 | doi = 10.1182/blood-2009-04-218503 | doi-access = free }}</ref>

Inherited [[bone marrow failure]] syndromes represent a kind of premature aging of the bone marrow. In people with these syndromes and in older adults, mutations associated with [[clonal hematopoiesis]] may arise as an adaptive response to a progressively deteriorating hematopoietic niche, i.e., a depleting pool of [[Hematopoietic stem cells]]. The mutated stem cells then acquire a self-renewal advantage.<ref>{{cite journal |vauthors=Hall T, Gurbuxani S, Crispino JD |title=Malignant progression of preleukemic disorders |journal=Blood |volume=143 |issue=22 |pages=2245–55 |date=May 2024 |pmid=38498034 |doi=10.1182/blood.2023020817 }}</ref>

[[Chronic myelogenous leukemia]] is associated with a genetic abnormality called the [[Philadelphia chromosome|Philadelphia translocation]]; 95% of people with CML carry the Philadelphia mutation, although this is not exclusive to CML and can be observed in people with other types of leukemia.<ref>{{cite journal | vauthors = Salesse S, Verfaillie CM | title = BCR/ABL: from molecular mechanisms of leukemia induction to treatment of chronic myelogenous leukemia | journal = Oncogene | volume = 21 | issue = 56 | pages = 8547–59 | date = December 2002 | pmid = 12476301 | doi = 10.1038/sj.onc.1206082 | doi-access = free }}</ref><ref>{{Cite web|url=https://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=44179|title=NCI Dictionary of Cancer Terms|website=National Cancer Institute|language=en|access-date=15 February 2017|url-status=live|archive-url=https://web.archive.org/web/20170216141643/https://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=44179|archive-date=16 February 2017|date=2 February 2011}}</ref><ref>{{Cite web|url=https://www.cancer.org/cancer/chronic-myeloid-leukemia/causes-risks-prevention/what-causes.html|title=Do We Know What Causes Chronic Myeloid Leukemia?|website=www.cancer.org|access-date=15 February 2017|url-status=live|archive-url=https://web.archive.org/web/20170216144606/https://www.cancer.org/cancer/chronic-myeloid-leukemia/causes-risks-prevention/what-causes.html|archive-date=16 February 2017}}</ref><ref>{{Cite web|url=http://www.macmillan.org.uk/information-and-support/leukaemia/leukaemia-chronic-myeloid/understanding-cancer/what-is-leukaemia.html|title=What is chronic myeloid leukaemia? (CML) — Understanding — Macmillan Cancer Support|website=www.macmillan.org.uk|language=en|access-date=15 February 2017|url-status=live|archive-url=https://web.archive.org/web/20170216133037/http://www.macmillan.org.uk/information-and-support/leukaemia/leukaemia-chronic-myeloid/understanding-cancer/what-is-leukaemia.html|archive-date=16 February 2017}}</ref>

===Non-ionizing radiation===
Whether or not non-ionizing radiation causes leukemia has been studied for several decades. The [[International Agency for Research on Cancer]] expert working group undertook a detailed review of all data on static and [[extremely low frequency]] electromagnetic energy, which occurs naturally and in association with the generation, transmission, and use of electrical power.<ref name="isbn92-832-1280-0">{{cite book|title=Non-Ionizing Radiation, Part 1: Static and Extremely Low-Frequency (ELF) Electric and Magnetic Fields (IARC Monographs on the Evaluation of the Carcinogenic Risks)|publisher=World Health Organisation|location=Geneva|year=2002|pages=332–3, 338|isbn=978-92-832-1280-5|url=http://monographs.iarc.fr/ENG/Monographs/vol80/index.php|url-status=live|archive-url=https://web.archive.org/web/20081206231737/http://monographs.iarc.fr/ENG/Monographs/vol80/index.php|archive-date=6 December 2008}}</ref> They concluded that there is limited evidence that high levels of [[Extremely low frequency|ELF]] magnetic (but not electric) fields might cause some cases of [[childhood leukemia]].<ref name="isbn92-832-1280-0" /> No evidence for a relationship to leukemia or another form of malignancy in adults has been demonstrated.<ref name="isbn92-832-1280-0" /> Since exposure to such levels of ELFs is relatively uncommon, the [[World Health Organization]] concludes that ELF exposure, if later proven to be causative, would account for just 100 to 2400 cases worldwide each year, representing 0.2 to 4.9% of the total incidence of childhood leukemia for that year (about 0.03 to 0.9% of all leukemias).<ref name="urlWHO | Electromagnetic fields and public health">{{cite web|url=https://www.who.int/mediacentre/factsheets/fs322/en/index.html|title=WHO &#124; Electromagnetic fields and public health|access-date=18 February 2009|url-status=dead|archive-url=https://web.archive.org/web/20090216160809/http://www.who.int/mediacentre/factsheets/fs322/en/index.html|archive-date=16 February 2009}}</ref>