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URL of this page: https://medlineplus.gov/genetics/condition/cytogenetically-normal-acute-myeloid-leukemia/

Cytogenetically normal acute myeloid leukemia

Description

Cytogenetically normal acute myeloid leukemia (CN-AML) is a form of acute myeloid leukemia (AML). AML is a cancer of the myeloid cells, which are found in the blood and blood-forming tissue (bone marrow). AML is considered acute because it can worsen quickly.

In normal bone marrow, cells called hematopoietic stem cells develop into several types of mature blood cells:

  • White blood cells, which protect the body from infection (includes some myeloid cells)
  • Red blood cells, which carry oxygen
  • Platelets, which are involved in blood clotting

In people with CN-AML, the bone marrow makes large numbers of abnormal, immature white blood cells called myeloid blasts. The large number of abnormal cells crowds the bone marrow and interferes with the growth and development of healthy cells, including white blood cells, red blood cells, and platelets. As a result, people with CN-AML have a shortage of all types of mature blood cells (bone marrow failure), which causes:

  • An increased risk of infections
  • Fever
  • Fatigue and weakness
  • Easy bruising and abnormal bleeding

Frequency

There are approximately 4.4 cases of AML per 100,000 individuals each year in the United States. Approximately 45 to 60 percent of people with AML have CN-AML.

Causes

Some people with AML have large chromosomal rearrangements. AML is classified as "cytogenetically normal" when standard testing does not detect large chromosomal abnormalities. However, in people with CN-AML, genetic testing of cancer cells often reveals changes within one or more genes. Identifying specific genetic changes can help predict the course and outcome of an individual’s CN-AML (prognosis) and determine the most appropriate therapies.

Genetic changes that contribute to disease are called pathogenic variants. Pathogenic variants in many different genes have been associated with CN-AML. The genes that are associated with CN-AML provide instructions for producing proteins that are involved in cell growth and division (proliferation), cell maturation (differentiation), and cell survival. The pathogenic variants in these genes are typically acquired during a person’s lifetime (somatic) and are only present in cancer cells.

Specific gene variants are associated with varying risks of developing CN-AML. Pathogenic variants in the following genes are common in people with CN-AML:

The somatic variants in these and other genes that are associated with CN-AML disrupt the proliferation, differentiation, or survival of hematopoietic stem cells. Sometimes, more than one of these processes is disrupted. These changes likely contribute to the overproduction of abnormal, immature white blood cells that is seen in people with CN-AML.

The protein produced from the FLT3 gene plays an important role in cell signaling pathways that are directly involved in cell proliferation and differentiation, while the protein produced from the CEBPA gene helps regulate gene activity (expression). The protein made from the NPM1 gene shuttles between the nucleus and the surrounding fluid (the cytoplasm). Through its interactions with other proteins, it plays an important role in tumor suppression, which means that it keeps cells from proliferating in an uncontrolled way. The proteins produced by the IDH1 and IDH2 genes help produce energy for bone marrow cells to grow and mature.

Typically, people with CN-AML have pathogenic variants in more than one gene. For example, affected individuals with a variant in the NPM1 gene also frequently have a somatic variant in the FLT3 gene, both of which are likely involved in the development of cancer. In addition, environmental factors such as smoking or exposure to radiation increase an individual's risk of developing CN-AML.

Learn more about the genes associated with Cytogenetically normal acute myeloid leukemia

Additional Information from NCBI Gene:

Inheritance

Because CN-AML is typically caused by somatic variants, it is not usually inherited. In rare cases, inherited pathogenic variants can increase the risk of developing CN-AML; this occurs with a condition called familial acute myeloid leukemia with mutated CEBPA.

Other Names for This Condition

  • Acute myelogenous leukemia with normal karyotype
  • CN-AML
  • NK-AML
  • Normal karyotype acute myeloid leukemia

Additional Information & Resources

Genetic Testing Information

Patient Support and Advocacy Resources

Clinical Trials

Catalog of Genes and Diseases from OMIM

Scientific Articles on PubMed

References

  • Arber DA, Orazi A, Hasserjian RP, Borowitz MJ, Calvo KR, Kvasnicka HM, Wang SA, Bagg A, Barbui T, Branford S, Bueso-Ramos CE, Cortes JE, Dal Cin P, DiNardo CD, Dombret H, Duncavage EJ, Ebert BL, Estey EH, Facchetti F, Foucar K, Gangat N, Gianelli U, Godley LA, Gokbuget N, Gotlib J, Hellstrom-Lindberg E, Hobbs GS, Hoffman R, Jabbour EJ, Kiladjian JJ, Larson RA, Le Beau MM, Loh ML, Lowenberg B, Macintyre E, Malcovati L, Mullighan CG, Niemeyer C, Odenike OM, Ogawa S, Orfao A, Papaemmanuil E, Passamonti F, Porkka K, Pui CH, Radich JP, Reiter A, Rozman M, Rudelius M, Savona MR, Schiffer CA, Schmitt-Graeff A, Shimamura A, Sierra J, Stock WA, Stone RM, Tallman MS, Thiele J, Tien HF, Tzankov A, Vannucchi AM, Vyas P, Wei AH, Weinberg OK, Wierzbowska A, Cazzola M, Dohner H, Tefferi A. International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: integrating morphologic, clinical, and genomic data. Blood. 2022 Sep 15;140(11):1200-1228. doi: 10.1182/blood.2022015850. Citation on PubMed
  • Archer KJ, Fu H, Mrozek K, Nicolet D, Mims AS, Uy GL, Stock W, Byrd JC, Hiddemann W, Braess J, Spiekermann K, Metzeler KH, Herold T, Eisfeld AK. Identifying long-term survivors and those at higher or lower risk of relapse among patients with cytogenetically normal acute myeloid leukemia using a high-dimensional mixture cure model. J Hematol Oncol. 2024 May 3;17(1):28. doi: 10.1186/s13045-024-01553-6. Citation on PubMed
  • Dohner H, Wei AH, Appelbaum FR, Craddock C, DiNardo CD, Dombret H, Ebert BL, Fenaux P, Godley LA, Hasserjian RP, Larson RA, Levine RL, Miyazaki Y, Niederwieser D, Ossenkoppele G, Rollig C, Sierra J, Stein EM, Tallman MS, Tien HF, Wang J, Wierzbowska A, Lowenberg B. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022 Sep 22;140(12):1345-1377. doi: 10.1182/blood.2022016867. Citation on PubMed
  • Dohner H, Wei AH, Lowenberg B. Towards precision medicine for AML. Nat Rev Clin Oncol. 2021 Sep;18(9):577-590. doi: 10.1038/s41571-021-00509-w. Epub 2021 May 18. Citation on PubMed
  • Dohner H. Implication of the molecular characterization of acute myeloid leukemia. Hematology Am Soc Hematol Educ Program. 2007:412-9. doi: 10.1182/asheducation-2007.1.412. Citation on PubMed
  • Fernandez-Mercado M, Yip BH, Pellagatti A, Davies C, Larrayoz MJ, Kondo T, Perez C, Killick S, McDonald EJ, Odero MD, Agirre X, Prosper F, Calasanz MJ, Wainscoat JS, Boultwood J. Mutation patterns of 16 genes in primary and secondary acute myeloid leukemia (AML) with normal cytogenetics. PLoS One. 2012;7(8):e42334. doi: 10.1371/journal.pone.0042334. Epub 2012 Aug 9. Citation on PubMed
  • Kayser S, Levis MJ. The clinical impact of the molecular landscape of acute myeloid leukemia. Haematologica. 2023 Feb 1;108(2):308-320. doi: 10.3324/haematol.2022.280801. Citation on PubMed
  • Khoury JD, Solary E, Abla O, Akkari Y, Alaggio R, Apperley JF, Bejar R, Berti E, Busque L, Chan JKC, Chen W, Chen X, Chng WJ, Choi JK, Colmenero I, Coupland SE, Cross NCP, De Jong D, Elghetany MT, Takahashi E, Emile JF, Ferry J, Fogelstrand L, Fontenay M, Germing U, Gujral S, Haferlach T, Harrison C, Hodge JC, Hu S, Jansen JH, Kanagal-Shamanna R, Kantarjian HM, Kratz CP, Li XQ, Lim MS, Loeb K, Loghavi S, Marcogliese A, Meshinchi S, Michaels P, Naresh KN, Natkunam Y, Nejati R, Ott G, Padron E, Patel KP, Patkar N, Picarsic J, Platzbecker U, Roberts I, Schuh A, Sewell W, Siebert R, Tembhare P, Tyner J, Verstovsek S, Wang W, Wood B, Xiao W, Yeung C, Hochhaus A. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia. 2022 Jul;36(7):1703-1719. doi: 10.1038/s41375-022-01613-1. Epub 2022 Jun 22. Citation on PubMed
  • Marcucci G, Haferlach T, Dohner H. Molecular genetics of adult acute myeloid leukemia: prognostic and therapeutic implications. J Clin Oncol. 2011 Feb 10;29(5):475-86. doi: 10.1200/JCO.2010.30.2554. Epub 2011 Jan 10. Citation on PubMed
  • Mawad R, Estey EH. Acute myeloid leukemia with normal cytogenetics. Curr Oncol Rep. 2012 Oct;14(5):359-68. doi: 10.1007/s11912-012-0252-x. Citation on PubMed
  • Ningombam A, Verma D, Kumar R, Singh J, Ali MS, Pandey AK, Singh I, Bakhshi S, Sharma A, Pushpam D, Palanichamy JK, Tanwar P, Singh AR, Chopra A. Prognostic relevance of NPM1, CEBPA, and FLT3 mutations in cytogenetically normal adult AML patients. Am J Blood Res. 2023 Feb 15;13(1):28-43. eCollection 2023. Citation on PubMed
  • Park HS. What is new in acute myeloid leukemia classification? Blood Res. 2024 Apr 15;59(1):15. doi: 10.1007/s44313-024-00016-8. Citation on PubMed
  • Pastore F, Pastore A, Rothenberg-Thurley M, Metzeler KH, Ksienzyk B, Schneider S, Bohlander SK, Braess J, Sauerland MC, Gorlich D, Berdel WE, Wormann B, von Bergwelt-Baildon MS, Hiddemann W, Spiekermann K. Molecular profiling of patients with cytogenetically normal acute myeloid leukemia and hyperleukocytosis. Cancer. 2022 Dec 15;128(24):4213-4222. doi: 10.1002/cncr.34495. Epub 2022 Oct 22. Citation on PubMed
  • Sanders MA, Valk PJ. The evolving molecular genetic landscape in acute myeloid leukaemia. Curr Opin Hematol. 2013 Mar;20(2):79-85. doi: 10.1097/MOH.0b013e32835d821c. Citation on PubMed
  • Snaith O, Poveda-Rogers C, Laczko D, Yang G, Morrissette JJD. Cytogenetics and genomics of acute myeloid leukemia. Best Pract Res Clin Haematol. 2024 Mar;37(1):101533. doi: 10.1016/j.beha.2023.101533. Epub 2023 Dec 10. Citation on PubMed
  • Tsui SP, Ip HW, Saw NY, Zhang C, Cheung AK, Ng NK, Man CH, Lam SS, Tang WF, Lin CH, Cheng GH, Au CH, Ma ES, Chan TL, So JC, Ng MH, Cheng KC, Wong KF, Siu LP, Yip SF, Lin SY, Lau JS, Luk TH, Lee HK, Lau CK, Kho B, Sim JP, Kwong YL, Leung SY, Javed A, Leung AY. Redefining prognostication of de novo cytogenetically normal acute myeloid leukemia in young adults. Blood Cancer J. 2020 Oct 19;10(10):104. doi: 10.1038/s41408-020-00373-4. No abstract available. Citation on PubMed
  • Vakiti A, Reynolds SB, Mewawalla P. Acute Myeloid Leukemia. 2024 Apr 27. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK507875/ Citation on PubMed
  • Welch JS, Ley TJ, Link DC, Miller CA, Larson DE, Koboldt DC, Wartman LD, Lamprecht TL, Liu F, Xia J, Kandoth C, Fulton RS, McLellan MD, Dooling DJ, Wallis JW, Chen K, Harris CC, Schmidt HK, Kalicki-Veizer JM, Lu C, Zhang Q, Lin L, O'Laughlin MD, McMichael JF, Delehaunty KD, Fulton LA, Magrini VJ, McGrath SD, Demeter RT, Vickery TL, Hundal J, Cook LL, Swift GW, Reed JP, Alldredge PA, Wylie TN, Walker JR, Watson MA, Heath SE, Shannon WD, Varghese N, Nagarajan R, Payton JE, Baty JD, Kulkarni S, Klco JM, Tomasson MH, Westervelt P, Walter MJ, Graubert TA, DiPersio JF, Ding L, Mardis ER, Wilson RK. The origin and evolution of mutations in acute myeloid leukemia. Cell. 2012 Jul 20;150(2):264-78. doi: 10.1016/j.cell.2012.06.023. Citation on PubMed or Free article on PubMed Central
  • Yang L, Zhang H, Yang X, Lu T, Ma S, Cheng H, Yen K, Cheng T. Prognostic Prediction of Cytogenetically Normal Acute Myeloid Leukemia Based on a Gene Expression Model. Front Oncol. 2021 May 27;11:659201. doi: 10.3389/fonc.2021.659201. eCollection 2021. Citation on PubMed

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