Chronic myelogenous leukemia overview: Difference between revisions
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==Overview== | ==Overview== | ||
'''Chronic myelogenous leukemia''' ('''CML''') is a form of [[leukemia]] characterized by the increased and unregulated growth of predominantly [[myeloid]] cells in the [[bone marrow]] and the accumulation of these cells in the blood. CML is a clonal bone marrow [[stem cell]] disorder in which proliferation of mature [[granulocyte]]s ([[neutrophil]]s, [[eosinophil]]s, and [[basophil]]s) and their precursors is the main finding. It is a type of [[myeloproliferative disease]] associated with a characteristic [[chromosomal translocation]] called the [[Philadelphia chromosome]]. Historically, it has been treated with [[chemotherapy]], [[interferon]], [[bone marrow transplantation]], and[[targeted therapy|targeted therapies]], which was introduced at the beginning of the 21st century and have radically changed the management of chronic myelogenous leukemia.In 1960, the association of [[Philadelphia chromosome]] with the pathogenesis of chronic myelogenous leukemia was first discovered. In 1973, (9;22) translocation was first discovered. Chronic myelogenous leukemia may be classified according to the hematologic characteristics and laboratory findings into five subtypes. Chronic myelogenous leukemia is caused by a mutation in ''[[BCR|BCR-ABL]]'' gene. The most potent risk factor in the development of chronic myelogenous leukemia is [[ionizing radiation]]; for example, increased rates of CML were seen in people exposed to the atomic bombings of Hiroshima and Nagasaki. According to the American Cancer Society, screening for chronic myelogenous leukemia is not recommended. Chronic myelogenous leukemia must be differentiated from [[leukemoid reaction]], [[chronic neutrophilic leukemia]], and [[acute myeloid leukemia]]. Medical therapies for chronic myelogenous leukemia include chemotherapy, stem cell transplant , and/or biological therapy. <ref name="cancergov">National Cancer Institute. Physician Data Query Database 2015.http://www.cancer.gov/types/leukemia/hp/cml-treatment-pdq#section/_19</ref><ref name="cancerorg">American Cancer Society.2015.http://www.cancer.org/cancer/leukemia-chronicmyeloidcml/detailedguide/leukemia-chronic-myeloid-myelogenous-detection</ref><ref name="pmid24839370">{{cite journal| author=Gajendra S, Gupta R, Chandgothia M, Kumar L, Gupta R, Chavan SM| title=Chronic Neutrophilic Leukemia with V617F JAK2 Mutation. | journal=Indian J Hematol Blood Transfus | year= 2014 | volume= 30 | issue= 2 | pages= 139-42 | pmid=24839370 | doi=10.1007/s12288-012-0203-6 | pmc=PMC4022913 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24839370 }} | '''Chronic myelogenous leukemia''' ('''CML''') is a form of [[leukemia]] characterized by the increased and unregulated growth of predominantly [[myeloid]] cells in the [[bone marrow]] and the accumulation of these cells in the blood. CML is a clonal bone marrow [[stem cell]] disorder in which proliferation of mature [[granulocyte]]s ([[neutrophil]]s, [[eosinophil]]s, and [[basophil]]s) and their precursors is the main finding. It is a type of [[myeloproliferative disease]] associated with a characteristic [[chromosomal translocation]] called the [[Philadelphia chromosome]]. Historically, it has been treated with [[chemotherapy]], [[interferon]], [[bone marrow transplantation]], and[[targeted therapy|targeted therapies]], which was introduced at the beginning of the 21st century and have radically changed the management of chronic myelogenous leukemia.In 1960, the association of [[Philadelphia chromosome]] with the pathogenesis of chronic myelogenous leukemia was first discovered. In 1973, (9;22) translocation was first discovered. Chronic myelogenous leukemia may be classified according to the hematologic characteristics and laboratory findings into five subtypes. Chronic myelogenous leukemia is caused by a mutation in ''[[BCR|BCR-ABL]]'' gene. The most potent risk factor in the development of chronic myelogenous leukemia is [[ionizing radiation]]; for example, increased rates of CML were seen in people exposed to the atomic bombings of Hiroshima and Nagasaki. According to the American Cancer Society, screening for chronic myelogenous leukemia is not recommended. Chronic myelogenous leukemia must be differentiated from [[leukemoid reaction]], [[chronic neutrophilic leukemia]], and [[acute myeloid leukemia]]. Medical therapies for chronic myelogenous leukemia include chemotherapy, stem cell transplant , and/or biological therapy. <ref name="cancergov">National Cancer Institute. Physician Data Query Database 2015.http://www.cancer.gov/types/leukemia/hp/cml-treatment-pdq#section/_19</ref><ref name="cancerorg">American Cancer Society.2015.http://www.cancer.org/cancer/leukemia-chronicmyeloidcml/detailedguide/leukemia-chronic-myeloid-myelogenous-detection</ref><ref name="pmid24839370">{{cite journal| author=Gajendra S, Gupta R, Chandgothia M, Kumar L, Gupta R, Chavan SM| title=Chronic Neutrophilic Leukemia with V617F JAK2 Mutation. | journal=Indian J Hematol Blood Transfus | year= 2014 | volume= 30 | issue= 2 | pages= 139-42 | pmid=24839370 | doi=10.1007/s12288-012-0203-6 | pmc=PMC4022913 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24839370 }} </ref><ref name="Goldman2010">{{cite journal|last1=Goldman|first1=John M.|title=Chronic Myeloid Leukemia: A Historical Perspective|journal=Seminars in Hematology|volume=47|issue=4|year=2010|pages=302–311|issn=00371963|doi=10.1053/j.seminhematol.2010.07.001}}</ref><ref name="pmid3332855">{{cite journal| author=Shepherd PC, Ganesan TS, Galton DA| title=Haematological classification of the chronic myeloid leukaemias. | journal=Baillieres Clin Haematol | year= 1987 | volume= 1 | issue= 4 | pages= 887-906 | pmid=3332855 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3332855 }} </ref><ref name="pmid3477299">{{cite journal| author=Moloney WC| title=Radiogenic leukemia revisited. | journal=Blood | year= 1987 | volume= 70 | issue= 4 | pages= 905-8 | pmid=3477299 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3477299 }} </ref> | ||
==Historical Perspective== | ==Historical Perspective== | ||
Revision as of 21:59, 22 October 2015
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mohamad Alkateb, MBBCh [2]
Overview
Chronic myelogenous leukemia (CML) is a form of leukemia characterized by the increased and unregulated growth of predominantly myeloid cells in the bone marrow and the accumulation of these cells in the blood. CML is a clonal bone marrow stem cell disorder in which proliferation of mature granulocytes (neutrophils, eosinophils, and basophils) and their precursors is the main finding. It is a type of myeloproliferative disease associated with a characteristic chromosomal translocation called the Philadelphia chromosome. Historically, it has been treated with chemotherapy, interferon, bone marrow transplantation, andtargeted therapies, which was introduced at the beginning of the 21st century and have radically changed the management of chronic myelogenous leukemia.In 1960, the association of Philadelphia chromosome with the pathogenesis of chronic myelogenous leukemia was first discovered. In 1973, (9;22) translocation was first discovered. Chronic myelogenous leukemia may be classified according to the hematologic characteristics and laboratory findings into five subtypes. Chronic myelogenous leukemia is caused by a mutation in BCR-ABL gene. The most potent risk factor in the development of chronic myelogenous leukemia is ionizing radiation; for example, increased rates of CML were seen in people exposed to the atomic bombings of Hiroshima and Nagasaki. According to the American Cancer Society, screening for chronic myelogenous leukemia is not recommended. Chronic myelogenous leukemia must be differentiated from leukemoid reaction, chronic neutrophilic leukemia, and acute myeloid leukemia. Medical therapies for chronic myelogenous leukemia include chemotherapy, stem cell transplant , and/or biological therapy. [1][2][3][4][5][6]
Historical Perspective
In the 1840s, the first cases of chronic myelogenous leukemia (splenomegaly with high leukocyte count) was reported in France, Germany, and Scotland. In 1960, the association of Philadelphia chromosome with the pathogenesis of chronic myelogenous leukemia was first discovered. In 1973, (9;22) translocation was first discovered.[4]
Classification
Chronic myelogenous leukemia may be classified according to the hematologic characteristics and laboratory findings into five subtypes: chronic granulocytic leukaemia (CGL), juvenile chronic myelogenous leukemia, chronic neutrophilic leukaemia (CNL), chronic myelomonocytic leukaemia (CMML) ,and atypical chronic myelogenous leukemia (aCML).[5]
Pathophysiology
Genes involved in the pathogenesis of chronic myelogenous leukemia include ''BCR'' and ''ABL''. [7]
Causes
Chronic myelogenous leukemia is caused by a mutation in BCR-ABL gene.[1]
Differentiating Chronic myelogenous leukemia from other Diseases
Chronic myelogenous leukemia must be differentiated from leukemoid reaction, chronic neutrophilic leukemia, and acute myeloid leukemia.[3]
Epidemiology and Demographics
Chronic myelogenous leukemia (CML) occurs in all age groups, but most commonly in the middle-aged and elderly. Chronic myelogenous leukemia affects slightly more men than women. chronic myelogenous leukemia represents about 15–20% of all cases of adult leukemia in Western populations.[8] In 2011, the age-adjusted incidence of chronic myelogenous leukemia was 1.81 per 100,000 persons in the United States.[9]
Risk factors
The most potent risk factor in the development of chronic myelogenous leukemia is ionizing radiation; for example, increased rates of CML were seen in people exposed to the atomic bombings of Hiroshima and Nagasaki. Other risk factors include formaldehyde, obesity, and smoking.[6][10]
Screening
According to the American Cancer Society, screening for chronic myelogenous leukemia is not recommended.[2]
Natural History, Complications and Prognosis
If left untreated, majority of patients with chronic myelogenous leukemia may progress to develop fever, night sweats, and fatigue. Common complications of chronic myelogenous leukemia include bleeding and anemia. Prognosis is generally poor, and the 5-year survival rate of patients with chronic myelogenous leukemia is approximately 59.9%.[9][1]
Diagnosis
Staging
Chronic myelogenous leukemia may be classified according to the clinical characteristics and laboratory findings into three subtypes: chronic phase, accelerated phase, and blast crisis. [10][11]
History and Symptoms
Patients are often asymptomatic at diagnosis. However, if symptoms present, symptoms of chronic myelogenous leukemia include fever, fatigue, and bleeding.[10]
Physical Examination
Patients with chronic myelogenous leukemia are usually well-appearing. Physical examination of patients with chronic myelogenous leukemia is usually remarkable for skin bruising, fever, splenomegaly, and lymphadenopathy.
Laboratory Findings
Laboratory findings consistent with the diagnosis of chronic myelogenous leukemia include leukocytosis, thrombocytopenia, and anemia.[10]
Chest X-Ray
Chest x-ray may be helpful in the diagnosis of chronic myelogenous leukemia. Findings on chest x-ray suggestive of chronic myelogenous leukemia include enlarged mediastinal lymph nodes, enlarged thymus gland, and pneumonia.[10]
Abdominal CT
Abdominal and chest CT scan may be helpful in the diagnosis of chronic myelogenous leukemia. Findings on CT scan suggestive of chronic myelogenous leukemia include enlarged lymph nodes.[10]
Brain MRI
Brain MRI may be helpful in the detection of brain metastasis in patients with chronic myelogenous leukemia.[10]
Abdominal Ultrasound
Abdominal ultrasound may be helpful in the diagnosis of chronic myelogenous leukemia. Findings on abdominal ultrasound suggestive of chronic myelogenous leukemia include enlarged lymph nodes and splenomegaly.[10]
Other Diagnostic Studies
Other diagnostic studies for chronic myelogenous leukemia include bone marrow aspiration and biopsy, lumbar puncture, and lymph node biopsy.[10]
Treatment
Medical Therapy
Medical therapies for chronic myelogenous leukemia include chemotherapy, stem cell transplant , and/or biological therapy. With improved understanding of the nature of the bcr-abl protein and its action as a tyrosine kinase, targeted therapies have been developed (the first of which was imatinib mesylate) which specifically inhibit the activity of the bcr-abl protein. These tyrosine kinase inhibitors can induce complete remissions in chronic myelogenous leukemia, confirming the central importance of bcr-abl as the cause of chronic myelogenous leukemia.[1]
Surgery
Surgical intervention is recommended for the management of chronic myelogenous leukemia in case of splenectomy.[10]
Primary Prevention
There are no primary preventive measures available for chronic myelogenous leukemia.[2]
Secondary Prevention
There are no secondary preventive measures available for chronic myelogenous leukemia.
References
- ↑ 1.0 1.1 1.2 1.3 National Cancer Institute. Physician Data Query Database 2015.http://www.cancer.gov/types/leukemia/hp/cml-treatment-pdq#section/_19
- ↑ 2.0 2.1 2.2 American Cancer Society.2015.http://www.cancer.org/cancer/leukemia-chronicmyeloidcml/detailedguide/leukemia-chronic-myeloid-myelogenous-detection
- ↑ 3.0 3.1 Gajendra S, Gupta R, Chandgothia M, Kumar L, Gupta R, Chavan SM (2014). "Chronic Neutrophilic Leukemia with V617F JAK2 Mutation". Indian J Hematol Blood Transfus. 30 (2): 139–42. doi:10.1007/s12288-012-0203-6. PMC 4022913. PMID 24839370.
- ↑ 4.0 4.1 Goldman, John M. (2010). "Chronic Myeloid Leukemia: A Historical Perspective". Seminars in Hematology. 47 (4): 302–311. doi:10.1053/j.seminhematol.2010.07.001. ISSN 0037-1963.
- ↑ 5.0 5.1 Shepherd PC, Ganesan TS, Galton DA (1987). "Haematological classification of the chronic myeloid leukaemias". Baillieres Clin Haematol. 1 (4): 887–906. PMID 3332855.
- ↑ 6.0 6.1 Moloney WC (1987). "Radiogenic leukemia revisited". Blood. 70 (4): 905–8. PMID 3477299.
- ↑ Hehlmann R, Hochhaus A, Baccarani M; European LeukemiaNet (2007). "Chronic myeloid leukaemia". Lancet. 370 (9584): 342–50. PMID 17662883.
- ↑ Faderl S, Talpaz M, Estrov Z, Kantarjian HM (1999). "Chronic myelogenous leukemia: biology and therapy". Annals of Internal Medicine. 131 (3): 207–219. PMID 10428738.
- ↑ 9.0 9.1 Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z,Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2011/, based on November 2013 SEER data submission, posted to the SEER web site, April 2014.
- ↑ 10.0 10.1 10.2 10.3 10.4 10.5 10.6 10.7 10.8 10.9 Canadian Cancer Society.2015.http://www.cancer.ca/en/cancer-information/cancer-type/leukemia-chronic-myelogenous-cml/staging/?region=ab
- ↑ Vardiman J, Harris N, Brunning R (2002). "The World Health Organization (WHO) classification of the myeloid neoplasms". Blood. 100 (7): 2292–302. PMID 12239137. Retrieved 2007-09-22.