Acute lymphoblastic leukemia pathophysiology: Difference between revisions
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{{CMG}} {{AE}} {{RT}}{{SM}} {{CLG}} | {{CMG}} {{AE}} {{RT}}{{SM}} {{CLG}} | ||
== Overview == | == Overview == | ||
Generally cancer is caused by damage to [[Deoxyribonucleic Acid|DNA]] that leads to uncontrolled cellular growth causing the development of acute lymphoblastic leukemia. Genetic mutations involved in the pathogenesis of acute lymphoblastic leukemia are related with [[chromosomal translocation]]s. Genes involved in the pathogenesis of acute limphoblastic leukemia include t(9;22)(q34;q11.2), t(v;11q23);, t(12;21)(p13;q22) ''TEL-AML1'', t(5;14)(q31;q32)''IL3-IGH'' and t(1;19)(q23;p13.3) ''TCF3-PBX1''. | Generally cancer is caused by damage to [[Deoxyribonucleic Acid|DNA]] that leads to uncontrolled cellular growth causing the development of acute lymphoblastic leukemia. Genetic mutations involved in the pathogenesis of acute lymphoblastic leukemia are related with [[chromosomal translocation]]s. Genes involved in the pathogenesis of acute limphoblastic leukemia include t(9;22)(q34;q11.2) ''BCR-ABL1'', t(v;11q23);, t(12;21)(p13;q22) ''TEL-AML1'', t(5;14)(q31;q32)''IL3-IGH'' and t(1;19)(q23;p13.3) ''TCF3-PBX1''. | ||
== Pathophysiology == | == Pathophysiology == | ||
The cause of most acute lymphoblastic leukemia is not known. In general, cancer is caused by damage to [[Deoxyribonucleic Acid|DNA]] that leads to uncontrolled cellular growth and spread throughout the body, either by increasing chemical signals that cause growth | The cause of most acute lymphoblastic leukemia is not known. In general, cancer is caused by damage to [[Deoxyribonucleic Acid|DNA]] that leads to uncontrolled cellular growth and spread throughout the body, either by increasing chemical signals that cause growth or interrupting chemical signals that control growth. This damage may be caused by environmental factors such as chemicals, drugs or radiation. | ||
In leukemias | In leukemias including acute lymphoblastic leukemia, [[chromosomal translocation]] occur regularly. It is thought that most translocations occur before birth during fetal development. These translocations may trigger [[oncogene]]s to "turn on", causing unregulated [[mitosis]] where cells divide too quickly and abnormally, resulting in leukemia. | ||
According with the [[World Health Organization]] (WHO) classification of acute lymphoblastic leukemia, B lymphoblastic leukemia/lymphoma with recurrent genetic abnormalities include: | According with the [[World Health Organization]] (WHO) classification of acute lymphoblastic leukemia, B lymphoblastic leukemia/lymphoma with recurrent genetic abnormalities include: | ||
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* ALL-L2: large varied cells | * ALL-L2: large varied cells | ||
* ALL-L3: large varied cells with [[vacuole]]s (bubble-like features) | * ALL-L3: large varied cells with [[vacuole]]s (bubble-like features) | ||
[[Malignant]], immature [[lymphoblasts|white blood cells]] continuously multiply and are overproduced in the [[bone marrow]]. Acute lymphoblastic leukemia causes damage and death by crowding out normal cells in the bone marrow, and by spreading ([[metastasis|metastasizing]]) to other organs. | [[Malignant]], immature [[lymphoblasts|white blood cells]] continuously multiply and are overproduced in the [[bone marrow]]. Acute lymphoblastic leukemia causes damage and death by crowding out normal cells in the bone marrow, and by spreading ([[metastasis|metastasizing]]) to other organs. | ||
==Markers== | ==Markers== | ||
B-cell | B-cell acute lymphoblastic leukemia:<ref name=ALL>{{cite web | title = National Cancer Institute| url =http://www.cancer.gov/types/leukemia/hp/adult-all-treatment-pdq }}</ref> | ||
:*Typically express [[CD10]], [[CD19]], and [[CD34]] on their surface along, with nuclear terminal deoxynucleotide transferase (TdT) | :*Typically express [[CD10]], [[CD19]], and [[CD34]] on their surface along, with nuclear terminal deoxynucleotide transferase (TdT) | ||
T-cell | T-cell acute lymphoblastic leukemia: | ||
:*Typically express [[CD2]], [[CD3]], [[CD7]], [[CD34]], and TdT. | :*Typically express [[CD2]], [[CD3]], [[CD7]], [[CD34]], and TdT. | ||
===Genetics=== | ===Genetics=== | ||
[[Cytogenetics]], the study of characteristic large changes in the [[chromosomes]] of [[cancer cell]]s, has been increasingly recognized as an important predictor of outcome in | [[Cytogenetics]], the study of characteristic large changes in the [[chromosomes]] of [[cancer cell]]s, has been increasingly recognized as an important predictor of outcome in acute lymphoblastic leukemia.<ref>{{cite journal |author=Moorman A, Harrison C, Buck G, Richards S, Secker-Walker L, Martineau M, Vance G, Cherry A, Higgins R, Fielding A, Foroni L, Paietta E, Tallman M, Litzow M, Wiernik P, Rowe J, Goldstone A, Dewald G |title=Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial |journal=Blood |volume=109 |issue=8 |pages=3189-97 |year=2007 |pmid=17170120}}</ref> | ||
It has been recognized for many years that some patients presenting with acute leukemia may have a cytogenetic abnormality that is cytogenetically indistinguishable from the Philadelphia chromosome (Ph1). This occurs in about 20% of adults and a small percentage of children with | It has been recognized for many years that some patients presenting with acute leukemia may have a cytogenetic abnormality that is cytogenetically indistinguishable from the Philadelphia chromosome (Ph1). This occurs in about 20% of adults and a small percentage of children with acute Lymphoblastic leukemia <ref name=ALL>{{cite web | title = National Cancer Institute| url =http://www.cancer.gov/types/leukemia/hp/adult-all-treatment-pdq }}</ref> | ||
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Revision as of 01:39, 31 August 2015
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Acute lymphoblastic leukemia Microchapters |
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Differentiating Acute lymphoblastic leukemia from other Diseases |
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Diagnosis |
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Treatment |
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Acute lymphoblastic leukemia pathophysiology On the Web |
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American Roentgen Ray Society Images of Acute lymphoblastic leukemia pathophysiology |
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Directions to Hospitals Treating Acute lymphoblastic leukemia |
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Risk calculators and risk factors for Acute lymphoblastic leukemia pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2]Shivali Marketkar, M.B.B.S. [3] Carlos A Lopez, M.D. [4]
Overview
Generally cancer is caused by damage to DNA that leads to uncontrolled cellular growth causing the development of acute lymphoblastic leukemia. Genetic mutations involved in the pathogenesis of acute lymphoblastic leukemia are related with chromosomal translocations. Genes involved in the pathogenesis of acute limphoblastic leukemia include t(9;22)(q34;q11.2) BCR-ABL1, t(v;11q23);, t(12;21)(p13;q22) TEL-AML1, t(5;14)(q31;q32)IL3-IGH and t(1;19)(q23;p13.3) TCF3-PBX1.
Pathophysiology
The cause of most acute lymphoblastic leukemia is not known. In general, cancer is caused by damage to DNA that leads to uncontrolled cellular growth and spread throughout the body, either by increasing chemical signals that cause growth or interrupting chemical signals that control growth. This damage may be caused by environmental factors such as chemicals, drugs or radiation.
In leukemias including acute lymphoblastic leukemia, chromosomal translocation occur regularly. It is thought that most translocations occur before birth during fetal development. These translocations may trigger oncogenes to "turn on", causing unregulated mitosis where cells divide too quickly and abnormally, resulting in leukemia.
According with the World Health Organization (WHO) classification of acute lymphoblastic leukemia, B lymphoblastic leukemia/lymphoma with recurrent genetic abnormalities include:
- B lymphoblastic leukemia/lymphoma with t(9;22)(q34;q11.2), BCR-ABL1
- B lymphoblastic leukemia/lymphoma with t(v;11q23); MLL rearranged
- B lymphoblastic leukemia/lymphoma with t(12;21)(p13;q22) TEL-AML1 (ETV6-RUNX1)
- B lymphoblastic leukemia/lymphoma with hyperdiploidy
- B lymphoblastic leukemia/lymphoma with hypodiploidy
- B lymphoblastic leukemia/lymphoma with t(5;14)(q31;q32) IL3-IGH
- B lymphoblastic leukemia/lymphoma with t(1;19)(q23;p13.3) TCF3-PBX1
According with the French-American-British (FAB) classification of acute lymphoblastic leukemia is divided into 3 subtypes:
- ALL-L1: small uniform cells
- ALL-L2: large varied cells
- ALL-L3: large varied cells with vacuoles (bubble-like features)
Malignant, immature white blood cells continuously multiply and are overproduced in the bone marrow. Acute lymphoblastic leukemia causes damage and death by crowding out normal cells in the bone marrow, and by spreading (metastasizing) to other organs.
Markers
B-cell acute lymphoblastic leukemia:[1]
T-cell acute lymphoblastic leukemia:
Genetics
Cytogenetics, the study of characteristic large changes in the chromosomes of cancer cells, has been increasingly recognized as an important predictor of outcome in acute lymphoblastic leukemia.[2]
It has been recognized for many years that some patients presenting with acute leukemia may have a cytogenetic abnormality that is cytogenetically indistinguishable from the Philadelphia chromosome (Ph1). This occurs in about 20% of adults and a small percentage of children with acute Lymphoblastic leukemia [1]
| Cytogenetic change | Risk category |
|---|---|
| Philadelphia chromosome | Poor prognosis |
| t(4;11)(q21;q23) | Poor prognosis |
| t(8;14)(q24.1;q32) | Poor prognosis |
| Complex karyotype (more than four abnormalities) | Poor prognosis |
| Low hypodiploidy or near triploidy | Poor prognosis |
| High hypodiploidy | Good prognosis |
| del(9p) | Good prognosis |
Gallery
References
- ↑ 1.0 1.1 "National Cancer Institute".
- ↑ Moorman A, Harrison C, Buck G, Richards S, Secker-Walker L, Martineau M, Vance G, Cherry A, Higgins R, Fielding A, Foroni L, Paietta E, Tallman M, Litzow M, Wiernik P, Rowe J, Goldstone A, Dewald G (2007). "Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial". Blood. 109 (8): 3189–97. PMID 17170120.