Ph+ CML Disease Overview

Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) is a disease caused by an abnormal fusion protein, BCR-ABL

Chronic myeloid leukemia (CML) is characterized by the presence of a Philadelphia (Ph) chromosome, which is a translocation of chromosomes 9 and 22.1,2 This translocation causes BCR and ABL genes to fuse. The BCR-ABL gene creates a fusion protein—the BCR-ABL protein—the molecular marker of CML, which continuously stimulates the cells to grow giving rise to the leukemic clone.2 This BCR-ABL protein is a constitutively active tyrosine kinase domain, which promotes cell proliferation.3 Evidence confirms that the unregulated activity of the ABL tyrosine kinase in BCR-ABL is the cause of Ph+ CML.4 For this reason, the BCR-ABL tyrosine kinase domain remains ideal for a targeted therapeutic approach.

Translocation of Chromosomes 9 and 221

Translocation of Chromosomes 9 and 22
The Philadelphia chromosome results from a reciprocal translocation of sections of chromosomes 9 and 22. This translocation fuses portions of the BCR and ABL genes, resulting in the BCR-ABL oncogene that encodes the BCR-ABL fusion protein. This BCR-ABL protein deregulates tyrosine kinase activity.1-4

Keeping Ph+ CML patients in the chronic phase is vital5

In ENESTnd, the median survival of patients who progressed to AP/BC was only 10.5 months, illustrating the importance of maintaining patients with Ph+ CML in the chronic phase.5,6

Survival after progression to AP/BC in ENESTnd
(n/N = 34/846)5*

Survival After CML Progression to AP/BC

*ENESTnd patients (N=846) were followed for survival and progression every 3 months; planned duration of follow-up is 10 years.5,6

AP/BC, accelerated phase/blast crisis; MMR, major molecular response.

ENESTnd is a Phase III, randomized, open-label, multicenter study of 846 patients with newly diagnosed Ph+ CML in chronic phase who received TASIGNA 300 mg BID, TASIGNA 400 mg BID, or imatinib 400 mg QD. The primary endpoint was MMR at 12 months.

  1. Faderl S, et al. N Engl J Med. 1999;341(3):164-172;
  2. Sawyers CL. N Engl J Med. 1999;340(17):1330-1340;
  3. Ren R. Nat Rev Cancer. 2005;5(3):172-183;
  4. Hochhaus A, et al. Leukemia. 2002;16(11):2190-2196;
  5. Larson RA, et al. Leukemia. 2012;26(10):2197-2203;
  6. TASIGNA® (nilotinib) Summary of Product Characteristics. Basel, Switzerland: Novartis Pharma AG; May 2017.