title: The Philadelphia chromosome in leukemogenesis.
abstract: The truncated chromosome 22 that results from the reciprocal translocation t(9;22)(q34;q11) is known as the Philadelphia chromosome (Ph) and is a hallmark of chronic myeloid leukemia (CML). In leukemia cells, Ph not only impairs the physiological signaling pathways but also disrupts genomic stability. This aberrant fusion gene encodes the breakpoint cluster region-proto-oncogene tyrosine-protein kinase (BCR-ABL1) oncogenic protein with persistently enhanced tyrosine kinase activity. The kinase activity is responsible for maintaining proliferation, inhibiting differentiation, and conferring resistance to cell death. During the progression of CML from the chronic phase to the accelerated phase and then to the blast phase, the expression patterns of different BCR-ABL1 transcripts vary. Each BCR-ABL1 transcript is present in a distinct leukemia phenotype, which predicts both response to therapy and clinical outcome. Besides CML, the Ph is found in acute lymphoblastic leukemia, acute myeloid leukemia, and mixed-phenotype acute leukemia. Here, we provide an overview of the clinical presentation and cellular biology of different phenotypes of Ph-positive leukemia and highlight key findings regarding leukemogenesis.
authors.affiliation: Department of Hematology, The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, 116023, Liaoning, P. R. China.|State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.
authors.forename: Zhi-Jie
authors.initials: ZJ
authors.lastname: Kang
authors.affiliation: Department of Hematology, The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, 116023, Liaoning, P. R. China.|State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.
authors.forename: Yu-Fei
authors.initials: YF
authors.lastname: Liu
authors.affiliation: Department of Oncology, The Second Affiliated Hospital, Dalian Medical University, Dalian, 116023, Liaoning, P. R. China.
authors.forename: Ling-Zhi
authors.initials: LZ
authors.lastname: Xu
authors.affiliation: Department of Hematology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, Guangdong, P. R. China.
authors.forename: Zi-Jie
authors.initials: ZJ
authors.lastname: Long
authors.affiliation: Department of Hematology, The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, 116023, Liaoning, P. R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Huang
authors.affiliation: Department of Hematology, The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, 116023, Liaoning, P. R. China.|State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Hematology, The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, 116023, Liaoning, P. R. China.|State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Hematology, The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, 116023, Liaoning, P. R. China.|State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.
authors.forename: Jiu-Xing
authors.initials: JX
authors.lastname: Feng
authors.affiliation: Department of Hematology, The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, 116023, Liaoning, P. R. China.|State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.
authors.forename: Yu-Jia
authors.initials: YJ
authors.lastname: Pan
authors.affiliation: Department of Hematology, The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, 116023, Liaoning, P. R. China. yanjsdmu@126.com.
authors.forename: Jin-Song
authors.initials: JS
authors.lastname: Yan
authors.affiliation: Department of Hematology, The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, 116023, Liaoning, P. R. China. liuq9@mail.sysu.edu.cn.|State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China. liuq9@mail.sysu.edu.cn.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Liu
mesh_terms: D063646:Carcinogenesis; D049109:Cell Proliferation; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D042822:Genomic Instability; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D000090063:Proto-Oncogene Mas
chemical_list: C581634:BCR-ABL1 fusion protein, human; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016044:Fusion Proteins, bcr-abl
keywords: BCR-ABL1; Chronic myeloid leukemia; Philadelphia chromosome; Signaling pathway; Translocations