PMID- 16522812 OWN - NLM STAT- MEDLINE DCOM- 20070817 LR - 20240324 IS - 0006-4971 (Print) IS - 1528-0020 (Electronic) IS - 0006-4971 (Linking) VI - 108 IP - 1 DP - 2006 Jul 1 TI - Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. PG - 28-37 AB - The introduction in 1998 of imatinib mesylate (IM) revolutionized management of patients with chronic myeloid leukemia (CML) and the second generation of tyrosine kinase inhibitors may prove superior to IM. Real-time quantitative polymerase chain reaction (RQ-PCR) provides an accurate measure of the total leukemiacell mass and the degree to which BCR-ABL transcripts are reduced by therapy correlates with progression-free survival. Because a rising level of BCR-ABL is an early indication of loss of response and thus the need to reassess therapeutic strategy, regular molecular monitoring of individual patients is clearly desirable. Here we summarize the results of a consensus meeting that took place at the National Institutes of Health (NIH) in Bethesda in October 2005. We make suggestions for (1) harmonizing the differing methodologies for measuring BCR-ABL transcripts in patients with CML undergoing treatment and using a conversion factor whereby individual laboratories can express BCR-ABL transcript levels on an internationally agreed scale; (2) using serial RQ-PCR results rather than bone marrow cytogenetics or fluorescence in situ hybridization (FISH) for the BCR-ABL gene to monitor individual patients responding to treatment; and (3) detecting and reporting Philadelphia (Ph) chromosome-positive subpopulations bearing BCR-ABL kinase domain mutations. We recognize that our recommendations are provisional and will require revision as new evidence emerges. FAU - Hughes, Timothy AU - Hughes T AD - Institute of Medical and Veterinary Science, Adelaide, Australia. FAU - Deininger, Michael AU - Deininger M FAU - Hochhaus, Andreas AU - Hochhaus A FAU - Branford, Susan AU - Branford S FAU - Radich, Jerald AU - Radich J FAU - Kaeda, Jaspal AU - Kaeda J FAU - Baccarani, Michele AU - Baccarani M FAU - Cortes, Jorge AU - Cortes J FAU - Cross, Nicholas C P AU - Cross NC FAU - Druker, Brian J AU - Druker BJ FAU - Gabert, Jean AU - Gabert J FAU - Grimwade, David AU - Grimwade D FAU - Hehlmann, Rudiger AU - Hehlmann R FAU - Kamel-Reid, Suzanne AU - Kamel-Reid S FAU - Lipton, Jeffrey H AU - Lipton JH FAU - Longtine, Janina AU - Longtine J FAU - Martinelli, Giovanni AU - Martinelli G FAU - Saglio, Giuseppe AU - Saglio G FAU - Soverini, Simona AU - Soverini S FAU - Stock, Wendy AU - Stock W FAU - Goldman, John M AU - Goldman JM LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20060307 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Protein Kinase Inhibitors) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.2 (Fusion Proteins, bcr-abl) SB - IM CIN - Blood. 2007 Mar 1;109(5):2263; author reply 2263-4. PMID: 17312000 MH - Drug Monitoring/*methods MH - Fusion Proteins, bcr-abl/*genetics MH - Humans MH - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis/drug therapy/*genetics MH - *Mutation MH - Protein Kinase Inhibitors/*therapeutic use MH - Protein Structure, Tertiary/genetics MH - Protein-Tyrosine Kinases/antagonists & inhibitors/*genetics MH - Reverse Transcriptase Polymerase Chain Reaction/methods/standards MH - Sensitivity and Specificity PMC - PMC1895821 EDAT- 2006/03/09 09:00 MHDA- 2007/08/19 09:00 PMCR- 2007/07/01 CRDT- 2006/03/09 09:00 PHST- 2006/03/09 09:00 [pubmed] PHST- 2007/08/19 09:00 [medline] PHST- 2006/03/09 09:00 [entrez] PHST- 2007/07/01 00:00 [pmc-release] AID - S0006-4971(20)64915-1 [pii] AID - 0028 [pii] AID - 10.1182/blood-2006-01-0092 [doi] PST - ppublish SO - Blood. 2006 Jul 1;108(1):28-37. doi: 10.1182/blood-2006-01-0092. Epub 2006 Mar 7.