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Chronic Myeloid Leukemia (CML) and Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL): Causes, Prevalence, and Treatment | Takeda Oncology


The Section Title

Leukemia is a blood cancer that develops in early blood-forming cells. There are four main types of leukemia – acute myeloid leukemia (AML), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL).

Chronic Myeloid Leukemia (CML)

Chronic myeloid leukemia (CML) – a rare form of leukemia – is a result of a genetic mutation that takes place in early, immature versions of myeloid cells, which form red blood cells, platelets and most types of white blood cells. 1

Subsequently, an abnormal gene called BCR-ABL1 forms, turning the damaged cell into a CML cell.1 CML typically progresses slowly through phases – the disease is most often diagnosed in chronic-phase (CP), but can move into accelerated-phase (AP) and blast-phase (BP) due to a number of factors. Approximately 90% of patients are diagnosed in CP-CML, but CML can progress to AP or BP, which are fast-growing and hard to treat. 2

Tens of thousands of people are diagnosed with leukemia each year, but only about 9,000 people in the U.S. are diagnosed with CML each year. 3

With five BCR-ABL1 tyrosine kinase inhibitors (TKIs) approved in the United States for the treatment of CP-CML, it is generally thought to be a manageable disease; however, if an early response to treatment is not achieved, outcomes are poor. 4 Even with available CML treatments, approximately 30% of patients do not survive five years.  5 This sobering statistic points to areas where improved care is needed.

The Section Title

  1 American Cancer Society. What Is Chronic Myeloid Leukemia? https://www.cancer.org/cancer/chronic-myeloid-leukemia/about/what-is-cml.htmlGo to https://www.cancer.org/cancer/chronic-myeloid-leukemia/about/what-is-cml.html. Accessed May 1, 2020.  2 Cancer.net. Leukemia – Chronic Myeloid – CML: Phases. https://www.cancer.net/cancer-types/leukemia-chronic-myeloid-cml/phasesGo to https://www.cancer.net/cancer-types/leukemia-chronic-myeloid-cml/phases. Accessed January 2021.  3American Cancer Society. Key Statistics for Chronic Myeloid Leukemia. https://www.cancer.org/cancer/chronic-myeloid-leukemia/about/statistics.htmlGo to https://www.cancer.org/cancer/chronic-myeloid-leukemia/about/statistics.html. Accessed April 2020. Cancer.net. Leukemia - Chronic Myeloid - CML: Types of Treatment. https://www.cancer.net/cancer-types/leukemia-chronic-myeloid-cml/types-treatmentGo to https://www.cancer.net/cancer-types/leukemia-chronic-myeloid-cml/types-treatment. Accessed January 2021.  4 SEER Cancer Stat Facts. National Cancer Institute. Bethesda, MD. Available at: https://seer.cancer.gov/statfacts/html/cmyl.htmlGo to https://seer.cancer.gov/statfacts/html/cmyl.html Accessed May 2021.  5 SEER Cancer Stat Facts. National Cancer Institute. Bethesda, MD. Available at: https://seer.cancer.gov/statfacts/html/cmyl.htmlGo to https://seer.cancer.gov/statfacts/html/cmyl.html Accessed May 2021.

Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL)

Acute lymphoblastic leukemia (ALL) is one of the four main types of leukemia; it starts from the early version of white blood cells, called lymphocytes, in the bone marrow. The term “acute” means that the leukemia can progress quickly and, if not treated, will likely be fatal within a few months.6,7

Philadelphia chromosome-positive (Ph+) ALL, a rare form of leukemia, is a subtype of ALL6, accounting for 25% of adults diagnosed with ALL and 3-5% of children diagnosed with ALL.8,9 There are over 9,000 new cases of adult Ph+ ALL diagnosed in the U.S. each year. 10,11

The abnormal formation of the Philadelphia chromosome, which occurs when pieces of chromosomes 9 and 22 switch with each other, leads to the development of BCR::ABL1 gene fusion. BCR::ABL1 gene fusion creates an abnormal protein that allows for leukemia cell growth.7

Ph+ ALL is a fast progressing and aggressive disease, and the long-term prognosis is poor. Individuals with Ph+ ALL typically have a worse prognosis than those with other subtypes of ALL.10,12 It is important that patients who are diagnosed with Ph+ ALL receive treatment as soon as possible.

  6 Leukemia and Lymphoma Society. https://www.lls.org/leukemia/acute-lymphoblastic-leukemiaGo to https://www.lls.org/leukemia/acute-lymphoblastic-leukemia. Accessed November 2023.  7 American Cancer Society https://www.lls.org/leukemia/acute-lymphoblastic-leukemia/childhood-all/all-subtypesGo to https://www.lls.org/leukemia/acute-lymphoblastic-leukemia/childhood-all/all-subtypes. Accessed November 2023.  8 Saleh K, Fernandez A, Pasquier F. Treatment of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia in Adults. Cancers (Basel). 2022;14(7):1805. doi: 10.3390/cancers14071805.  9 Kaczmarska A, Śliwa P, Zawitkowska J, et al. Genomic Analyses of Pediatric Acute Lymphoblastic Leukemia Ph+ and Ph-Like-Recent Progress in Treatment. Int J Mol Sci. 2021;22(12):6411. doi: 10.3390/ijms22126411.  10 Healio. https://www.healio.com/news/hematology-oncology/20200817/poor-ph-all-outcomes-require-reexamination-of-treatment-standardGo to https://www.healio.com/news/hematology-oncology/20200817/poor-ph-all-outcomes-require-reexamination-of-treatment-standard Accessed August 2023.  11 Data on File. Ph+ALL Epi Data. 2022.  12 Sasaki K, Jabbour E, Short NJ, et al. Acute lymphoblastic leukemia: A population-based study of outcome in the United States based on the surveillance, epidemiology, and end results (SEER) database, 1980-2017. Am J Hematol. 2021;96(6):650-658. doi:10.1002/ajh.26156.

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