Autochecked users, Comment administrators, Editors, Interface administrators, Reviewers, Suppressors, Administrators, Widget editors
1,874
edits
Changes
no edit summary
Brian Davis, PhD
Brian Davis, PhD
etc.
__TOC__
__TOC__
'''[http://www.ccga.io/index.php/Mixed_Phenotype_Acute_Leukemia_(MPAL)_with_t(9;22)(q34.1;q11.2);_BCR-ABL1 Mixed Phenotype Acute Leukemia (MPAL) with BCR-ABL1]'''
'''[http://www.ccga.io/index.php/HAEM5:Mixed-phenotype_acute_leukaemia_with_BCR::ABL1_fusion Mixed Phenotype Acute Leukemia (MPAL) with BCR-ABL1]'''
BCR-ABL1 translocations (Ph+) are more prevalent in adult vs. pediatric patients diagnosed as Mixed Phenotype Acute Leukemia (MPAL) [12,13]. The BCR-ABL1 translocations are considered to be prognostic of poorer outcomes in the context of patients diagnosed with Mixed Phenotype Acute Leukemia (MPAL) [12]. However, a number of individual studies indicate that Ph+ MPAL patients can be treated successfully wiht tyrosine kinase inhibitors (TKI) such as Imatinab and second generation TKIs [14,15].
BCR-ABL1 translocations (Ph+) are more prevalent in adult vs. pediatric patients diagnosed as Mixed Phenotype Acute Leukemia (MPAL) [12,13]. The BCR-ABL1 translocations are considered to be prognostic of poorer outcomes in the context of patients diagnosed with Mixed Phenotype Acute Leukemia (MPAL) [12]. However, a number of individual studies indicate that Ph+ MPAL patients can be treated successfully with tyrosine kinase inhibitors (TKI) such as Imatinab and second generation TKIs [14,15].
'''[http://www.ccga.io/index.php/Acute_Myeloid_Leukemia_(AML)_with_BCR-ABL1 Acute Myeloid Leukemia with BCR-ABL1]'''
'''[http://www.ccga.io/index.php/HAEM5:Acute_myeloid_leukaemia_with_BCR::ABL1_fusion Acute Myeloid Leukemia with BCR-ABL1]'''
This rare entity, accounting for <1% of AML and <1% of BCR-ABL1 positive acute and chronic leukemias, typically occurs in adults. AML with BCR-ABL1 is aggressive with poor response to traditional AML therapy or isolated tyrosine kinase (TK) therapy alone; TK therapy with subsequent allogeneic hematopoietic cell transplantation may improve survival [16].
This rare entity, accounting for <1% of AML and <1% of BCR-ABL1 positive acute and chronic leukemias, typically occurs in adults. AML with BCR-ABL1 is aggressive with poor response to traditional AML therapy or isolated tyrosine kinase (TK) therapy alone; TK therapy with subsequent allogeneic hematopoietic cell transplantation may improve survival [16].
==Gene Overview==
==Gene Overview==
The ''ABL1'' gene encodes a non-receptor tyrosine kinase that is ubiquitously expressed and involved in a large number of cellular processes (see '''[https://www.ncbi.nlm.nih.gov/gene/25#reference-sequences "NCBI Gene]'''). By far the most prevalent ''ABL1'' alteration associated with cancer are the fusions of the ''ABL1'' gene with a number of partners, but especially with the ''BCR'' gene in CML [1,2] and to a lesser extent in B-ALL and T-ALL.
The ''ABL1'' gene encodes a non-receptor tyrosine kinase that is ubiquitously expressed and involved in a large number of cellular processes (see '''[https://www.ncbi.nlm.nih.gov/gene/25#reference-sequences "NCBI Gene]'''). By far the most prevalent ''ABL1'' alteration associated with cancer are the fusions of the ''ABL1'' gene with a number of partners, but especially with the ''BCR'' gene in CML [1,2] and to a lesser extent in B-ALL and T-ALL. The head to tail arrangement of the BCR-ABL1 fusion gene results in an activated tyrosine kinase activity [6]. It appears that the N-terminal domain of ''BCR'' can cause oligomerization of the BCR-ABL1 protein product, thus activating the ''ABL1'' tyrosine kinase domain of the fusion protein [6,10,11]. The ''ABL1'' and ''ABL2'' genes encode tyrosine kinases which share overlapping physiological roles, and ''ABL2'' somatic or amplification mutations are more common than similar mutations in ''ABL1'' [6].
The head to tail arrangement of the BCR-ABL1 fusion gene results in an activated tyrosine kinase activity [6]. It appears that the N-terminal domain of ''BCR'' can cause oligomerization of the BCR-ABL1 protein product, thus activating the ''ABL1'' tyrosine kinase domain of the fusion protein [6,10,11].
The ''ABL1'' and ''ABL2'' genes encode tyrosine kinases which share overlapping physiological roles, and ''ABL2'' somatic or amplification mutations are more common than similar mutations in ''ABL1'' [6].
See the '''[http://www.ccga.io/index.php/BCR "BCR gene"]''' for additional details of the BCR-ABL1 gene fusion.
See the '''[http://www.ccga.io/index.php/BCR "BCR gene"]''' for additional details of the BCR-ABL1 gene fusion.
A number of other gene fusion partners have been identified with ''ABL1'' that are linked to hematological cancers, but at a much smaller prevalence than BCR-ABL1.
A number of other gene fusion partners have been identified with ''ABL1'' that are linked to hematological cancers, but at a much smaller prevalence than BCR-ABL1.
* NUP214-ABL1 (associated with T-cell Acute Lymphoblastic Leukemia).
*NUP214-ABL1 (associated with T-cell Acute Lymphoblastic Leukemia).
* ETV6-ABL1 (associated with Chronic Myeloid Leukemia, T-cell Acute Lymphoblastic Leukemia, B-cell Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia), and EML (associated with T-cell Acute Lymphoblastic Leukemia).
*ETV6-ABL1 (associated with Chronic Myeloid Leukemia, T-cell Acute Lymphoblastic Leukemia, B-cell Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia), and EML (associated with T-cell Acute Lymphoblastic Leukemia).
Somatic mutations for ''ABL1'' have been found in Lung Squamous Cell Carcinomas patients (2%), Uterine Corpus Endometrioid Carcinoma patients (3%) and in less than 1% of patients with Breast Invasive Carcinoma, Ovarian Serous Cystadenocarcinoma, and Lung Adenocarcinoma [6].
Somatic mutations for ''ABL1'' have been found in Lung Squamous Cell Carcinomas patients (2%), Uterine Corpus Endometrioid Carcinoma patients (3%) and in less than 1% of patients with Breast Invasive Carcinoma, Ovarian Serous Cystadenocarcinoma, and Lung Adenocarcinoma [6].
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
! Copy Number Loss !! Copy Number Gain !! LOH !! Loss-of-Function Mutation !! Gain-of-Function Mutation !! Translocation/Fusion
!Copy Number Loss!!Copy Number Gain!!LOH!!Loss-of-Function Mutation!!Gain-of-Function Mutation!!Translocation/Fusion
|-
|-
| || || || || X || X
| || || || ||X||X
|}
|}
'''[http://www.ccga.io/index.php/Acute_lymphoblastic_leukaemia_(ALL) Acute Lymphoblastic Leukemia]'''
'''[http://www.ccga.io/index.php/Acute_lymphoblastic_leukaemia_(ALL) Acute Lymphoblastic Leukemia]'''
'''[http://www.ccga.io/index.php/Acute_Myeloid_Leukemia_(AML)_with_BCR-ABL1 Acute Myeloid Leukemia (AML) with BCR-ABL1]'''
'''[http://www.ccga.io/index.php/HAEM5:Acute_myeloid_leukaemia_with_BCR::ABL1_fusion Acute Myeloid Leukemia (AML) with BCR-ABL1]'''
'''[http://www.ccga.io/index.php/Mixed_Phenotype_Acute_Leukemia_(MPAL)_with_t(9;22)(q34.1;q11.2);_BCR-ABL1 Mixed Phenotype Acute Leukemia (MPAL) with t(9;22)(q34.1;q11.2); BCR-ABL1]'''
'''[http://www.ccga.io/index.php/HAEM5:Mixed-phenotype_acute_leukaemia_with_BCR::ABL1_fusion Mixed Phenotype Acute Leukemia (MPAL) with t(9;22)(q34.1;q11.2); BCR-ABL1]'''
See the '''[http://www.ccga.io/index.php/BCR "BCR gene"]''' for additional details of the BCR-ABL1 gene fusion.
See the '''[http://www.ccga.io/index.php/BCR "BCR gene"]''' for additional details of the BCR-ABL1 gene fusion.
'''[http://www.genecards.org/cgi-bin/carddisp.pl?gene=abl1 ''ABL1'' by GeneCards]''' - general gene information and summaries
'''[http://www.genecards.org/cgi-bin/carddisp.pl?gene=abl1 ''ABL1'' by GeneCards]''' - general gene information and summaries
'''[https://www.ncbi.nlm.nih.gov/gene/25#reference-sequences''ABL1'' by NCBI Gene]''' - general gene information
'''[https://www.ncbi.nlm.nih.gov/gene/25#reference-sequences ''ABL1'' by NCBI Gene]''' - general gene information
'''[http://www.omim.org/entry/189980 ''ABL1'' by OMIM]''' - compendium of human genes and genetic phenotypes
'''[https://databases.lovd.nl/shared/genes/ABL1 ''ABL1'' by LOVD(3)]''' - Leiden Open Variation Database
'''[https://databases.lovd.nl/shared/genes/ABL1 ''ABL1'' by LOVD(3)]''' - Leiden Open Variation Database
'''[http://www.unav.es/genetica/TICdb/results.php?hgnc=ABL1 ''ABL1'' by TICdb]''' - database of Translocation breakpoints In Cancer
'''[http://www.unav.es/genetica/TICdb/results.php?hgnc=ABL1 ''ABL1'' by TICdb]''' - database of Translocation breakpoints In Cancer
16. Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. Revised 4th Edition. IARC Press: Lyon, France, p140.
16. Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. Revised 4th Edition. IARC Press: Lyon, France, p140.
== Notes ==
==Notes==
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.
[[Category:Cancer Genes A]]
[[Category:Cancer Genes A]]