PMID- 17970608
OWN - NLM
STAT- MEDLINE
DCOM- 20080110
LR  - 20230823
IS  - 1083-4087 (Print)
IS  - 1944-706X (Electronic)
IS  - 1083-4087 (Linking)
VI  - 13
IP  - 8 Suppl A
DP  - 2007 Oct
TI  - Chronic myeloid leukemia in 2007.
PG  - 4-7
LID - 10.18553/jmcp.2007.13.s8-a.4
AB  - BACKGROUND: Chronic myeloid leukemia (CML) is a potentially fatal stem cell 
      cancer that comprises approximately 14% of all leukemias. Although it is 
      estimated that 4,600 people will be diagnosed with CML in the United States in 
      2007, only 12% of those individuals will die from the disease. That low mortality 
      rate is due to the availability and efficacy of the new kinase inhibitors that 
      target the BCR-ABL oncogene and other targets to hold disease progression in 
      check. OBJECTIVE: To review the molecular pathogenesis of CML, describe the 
      clinical course of the disease, and explain the current application of 
      cytogenetics and molecular testing for diagnosis and treatment. SUMMARY: CML is 
      caused by the translocation of chromosomes 9 and 22 to create what is called the 
      Philadelphia chromosome. This translocation removes a critical regulatory domain 
      from the tyrosine kinase, ABL, such that its protein product is constitutively 
      active. This means that the cell escapes the constraints of normal cell growth 
      and proliferates uncontrollably. The modified protein is known as BCR-ABL, and it 
      causes CML by phosphorylating numerous downstream proteins involved in the 
      activation of cell division, among other functions. during the earliest phase of 
      the disease, the chronic phase, kinase inhibitors that target BCR-ABL are 
      effective in stopping disease progression. However, a minority of patients remain 
      unresponsive to this therapy. Laboratory tests are thus of great importance for 
      this disease. not only are they required for the diagnosis of CML, but during 
      therapy they can establish the degree of response. That response, in turn, can 
      supply the clinician with a good estimate of the prognosis for the patient. The 
      tests used for CML include complete blood count (CBC) with platelets, cytogenetic 
      analysis, fluorescence in situ hybridization (FISH), and quantitative polymerase 
      chain reaction (PCR). These tests vary in the difficulty of application and in 
      the sensitivity. CBC is commonplace within the average hospital laboratory, 
      whereas cytogenetic analysis, FISH, and PCR require specialized equipment, 
      personnel, and training. Hematologic counts are the least sensitive measures of 
      disease, with a limit of detection of a leukemic burden of 1011 cells. 
      Cytogenetics can detect a burden of 109 cells. Finally, quantitative PCr can 
      detect a burden of as few as 105 leukemic cells. The current costs of these tests 
      range from approximately $375 to $1,500 and must be performed every 3 to 6 months 
      to follow the patient's response to therapy. CONCLUSION: The advent of kinase 
      inhibitor therapy for CML has greatly increased the importance of sensitive 
      analysis of disease burden. Subsequent testing during therapy greatly improves 
      the ability of the clinician to predict the therapeutic outcome. Signs of early 
      treatment failure can give the patient time to switch therapies before the 
      disease progresses to an advanced stage.
FAU - Sessions, Jolynn
AU  - Sessions J
AD  - Emory University Hospital, Atlanta, GA, USA.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - J Manag Care Pharm
JT  - Journal of managed care pharmacy : JMCP
JID - 9605854
SB  - IM
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis/*genetics/therapy
MH  - Polymerase Chain Reaction
PMC - PMC10437355
EDAT- 2007/11/27 09:00
MHDA- 2008/01/11 09:00
PMCR- 2007/10/01
CRDT- 2007/11/27 09:00
PHST- 2007/11/27 09:00 [pubmed]
PHST- 2008/01/11 09:00 [medline]
PHST- 2007/11/27 09:00 [entrez]
PHST- 2007/10/01 00:00 [pmc-release]
AID - 2007(13)8: 4-7 [pii]
AID - 10.18553/jmcp.2007.13.s8-a.4 [doi]
PST - ppublish
SO  - J Manag Care Pharm. 2007 Oct;13(8 Suppl A):4-7. doi: 
      10.18553/jmcp.2007.13.s8-a.4.