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==Cancer Category/Type==
==Cancer Category/Type==
'''[http://www.ccga.io/index.php/Chronic_Myeloid_Leukemia_(CML)_with_t(9;22)(q34.1;q11.2);_BCR-ABL1 Chronic Myeloid Leukemia with BCR-ABL1]''' (also referred as (Chronic Myelogenous Leukemia))
'''[http://www.ccga.io/index.php/Chronic_Myeloid_Leukemia_(CML)_with_t(9;22)(q34.1;q11.2);_BCR-ABL1 Chronic Myeloid Leukemia with BCR-ABL1]''' (also referred as Chronic Myelogenous Leukemia)
More than 90% of patients diagnosed with Chronic Myeloid Leukemia bear a Philadelphia chromosome resulting from t(9;22)(q34.1;q11.2), which is a reciprocal translocation between chromosome 22 (''BCR'' locus) and chromosome 9 (''ABL1'' locus) (see '''[http://www.omim.org/entry/613065 OMIM]''') [1]. The Drug Imatinib mesylate, also known as Gleevec, was the one of the first molecularly developed drugs, and has a remarkably high success rate in treatment of patients with Chronic Myeloid Leukemia by targeting the BCR/ABL1 fusion product [5].
More than 90% of patients diagnosed with Chronic Myeloid Leukemia have a Philadelphia chromosome resulting from t(9;22)(q34.1;q11.2), which is a reciprocal translocation between chromosome 22 (''BCR'' locus) and chromosome 9 (''ABL1'' locus) (see '''[http://www.omim.org/entry/613065 OMIM]''') [1]. The Drug Imatinib mesylate, also known as Gleevec, was the one of the first molecularly developed drugs, and has a remarkably high success rate in treatment of patients with Chronic Myeloid Leukemia by targeting the BCR/ABL1 fusion product [5].
'''[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]'''
Approximately 20% of patients (25 - 30% of adults and 2 - 10% of children) diagnosed with Acute Lymphoblastic Leukemia bear a Philadelphia chromosome resulting from t(9;22)(q34.1;q11.2), which is a reciprocal translocation between chromosome 22 (''BCR'' locus) and chromosome 9 (''ABL1'' locus) (see '''[http://www.omim.org/entry/613065 OMIM]''') [1]. Treatment of Acute Lymphoblastic Leukemia patients with Gleevec does not have the same success as in Chronic Myeloid Leukemia patients because the genomic instability of ALL cells contributes to point mutations arising in the BRC-ABL1 kinase domain, leading to Gleevec resistance [4].
Approximately 20% of patients (25 - 30% of adults and 2 - 10% of children) diagnosed with Acute Lymphoblastic Leukemia have a Philadelphia chromosome resulting from t(9;22)(q34.1;q11.2), which is a reciprocal translocation between chromosome 22 (''BCR'' locus) and chromosome 9 (''ABL1'' locus) (see '''[http://www.omim.org/entry/613065 OMIM]''') [1]. Treatment of Acute Lymphoblastic Leukemia patients with Gleevec does not have the same success as in Chronic Myeloid Leukemia patients because the genomic instability of ALL cells contributes to point mutations arising in the BRC-ABL1 kinase domain, leading to Gleevec resistance [4].
'''[http://www.ccga.io/index.php/Acute_Myeloid_Leukemia_(AML)_with_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) [16,17]. The BCR-ABL1 translocations are considered to be prognostic of poorer outcomes in the context of patients diagnosed with Mixed Phenotype Acute Leukemia (MPAL) [16]. 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 [18,19].
BCR-ABL1 translocations (Ph+) are more prevalent in adult vs. pediatric patients diagnosed as Mixed Phenotype Acute Leukemia (MPAL) [16,17]. The BCR-ABL1 translocations are considered to be prognostic of poorer outcomes in the context of patients diagnosed with Mixed Phenotype Acute Leukemia (MPAL) [16]. 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 [18,19].
'''[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 [20].
==Gene Overview==
==Gene Overview==
'''[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/ABL1 "ABL1 gene"]''' for additional details of the BCR-ABL1 gene fusion.
See the '''[http://www.ccga.io/index.php/ABL1 "ABL1 gene"]''' for additional details of the BCR-ABL1 gene fusion.
'''[http://www.genecards.org/cgi-bin/carddisp.pl?gene=bcr ''BCR'' by GeneCards]''' - general gene information and summaries
'''[http://www.genecards.org/cgi-bin/carddisp.pl?gene=bcr ''BCR'' by GeneCards]''' - general gene information and summaries
'''[https://www.ncbi.nlm.nih.gov/gene/613 ''BCR'' by NCBI Gene]''' - general gene information and summaries
'''[http://omim.org/entry/151410 ''BCR'' by OMIM]''' - compendium of human genes and genetic phenotypes
'''[http://omim.org/entry/151410 ''BCR'' by OMIM]''' - compendium of human genes and genetic phenotypes
'''[https://databases.lovd.nl/shared/genes/BCR ''BCR'' by LOVD(3)]''' - Leiden Open Variation Database
'''[http://www.unav.es/genetica/TICdb/results.php?hgnc=BCR ''BCR'' by TICdb]''' - database of Translocation breakpoints In Cancer
==References==
==References==
19. Kawajiri C, et al., (2014). Successful treatment of Philadelphia chromosome-positive mixed phenotype acute leukemia by appropriate alternation of second-generation tyrosine kinase inhibitors according to BCR-ABL1 mutation status. Blood 99:513-518. PMID 24532437. DOI: 10.1007/s12185-014-1531-0.
19. Kawajiri C, et al., (2014). Successful treatment of Philadelphia chromosome-positive mixed phenotype acute leukemia by appropriate alternation of second-generation tyrosine kinase inhibitors according to BCR-ABL1 mutation status. Blood 99:513-518. PMID 24532437. DOI: 10.1007/s12185-014-1531-0.
20. 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 B]]