ALL in which the Philadelphia chromosome is present

The presence of the Philadelphia chromosome in patients with ALL is a poor prognostic factor:

• occurs in 20-30% of adult ALL and in 3% of childhood ALL (1)
  
  
• prior to the advent of tyrosine kinase inhibitors (TKI), Ph+ ALL was associated with a very poor prognosis despite the use of intensive chemotherapy and frequently hematopoietic stem-cell transplantation (HSCT) in first remission
  • development of TKIs revolutionized the therapy of Ph+ ALL. Addition of the first generation ABL1 class TKI imatinib to intensive chemotherapy dramatically increased the survival for children with Ph+ ALL and established that many patients can be cured without HSCT (2)
    
    
• in patients with ALL and a Philadelphia chromosome:
  • 1/3 - have M-bcr (major breakpoint-cluster region) rearrangements (resulting in a 210-kd protein) similar to those in patients with CML
  • 2/3 - have m-bcr (minor breakpoint-cluster region) rearrangements with a consequent 190-kd protein
  • outcome for patients with either variant is equally poor

Reference:

• Editorial.Acute lymphoblastic leukaemia - progress in children, less in adults.NEJM (1993);329:1343-44.
• Bernt KM, Hunger SP.Current Concepts in Pediatric Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia. Front Oncol. 2014 Mar 25;4:54.