Mayo Test Catalog, (Sorted By Test Name) - Mayo Medical ...

FBBCK
91664
t(9:22) BCR-ABL abnormality, resulting in formation of a fusion BCR-ABL mRNA and protein. The
ABL component of this oncoprotein contains tyrosine kinase activity and is thought to play a central role
in the proliferative phenotype of this leukemia. Recent advances have resulted in a number of therapeutic
drugs that inhibit the ABL tyrosine kinase, as well as other protein tyrosine kinases. Imatinib mesylate
(Gleevec, Novartis) is the prototype of these tyrosine kinase inhibitors (TKIs), which are capable of
inducing durable hematologic and (in most patients) cytogenetic remissions. Unfortunately, a significant
subset of patients can develop functional resistance to TKIs, due in a large number of tumors to the
acquisition of point mutations in the kinase domain (KD) of the chmeric ABL gene. To date, over 50
distinct mutations have been described, although 15 of these account for more than 80% of the mutations
encountered and have well documented in vitro or clinical resistance to TKIs. Recognition of TKI
resistance is important in CML, as the effect of some mutations can be overcome by increasing imatinib
dosage, whereas others require switching to either a different (second-generation) TKI, or alternative
therapy. The common T315I KD mutation is particularly important, given that this alteration confers
pan-resistance to all currently employed TKIs. Typically, TKI resistance is suspected in a CML patient
who shows loss of initial therapeutic response (eg, cytogenetic relapse), or a significant and sustained
increase in molecular BCR-ABL quantitative levels. Similar considerations are also present in patients
with Philadelphia chromosome positive (Ph+) B-cell acute lymphoblastic leukemia (ALL), who can also
be treated using TKI therapy. Point mutations in ABL are typically detected by direct sequencing of PCR
products, following RT-PCR amplification of the BCR-ABL mRNA transcript from a peripheral blood
specimen. However, direct sequencing has limited analytic sensitivity (approximately 20-30% mutant
alleles). In contrast, this test utilizes a novel strategy to detect 15 of the most common ABL KD mutations
accounting for > 80% of the most common and clinically important mutations. The sensitivity of this
ASPE/Luminex approach is enhanced, with a better lower limit of detection in the range of 5% to 8%
mutant alleles, with very high specificity.
Useful For: Evaluating patients with chronic myeloid leukemia and Philadelphia chromosome
positive B-cell acute lymphoblastic leukemia receiving tyrosine kinase inhibitor (TKI), therapy, who are
apparently failing treatment This is the preferred initial test to identify the presence of acquired
BCR-ABL mutations associated with TKI-resistance.
Interpretation: The presence of 1 or more point mutations in the translocated portion of the ABL
region of the BCR-ABL fusion mRNA is considered a positive result, indicating TKI (eg, imatinib)
resistance.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Hughes T, Deininger M, Hochhaus A, et al: Monitoring CML patients
responding to treatment with tyrosone kinase inhibitors: review and recommendations for harmonizing
current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for
expressing results. Blood 2006;108:28-37 2. Jabbour E, Kantarjian H, Jones D, et al: Frequency and
clinical significance of BCR-ABL mutations in patients with chronic myeloid leukemia treated with
imatinib mesylate. Leukemia 2006;20:1767-1773 3. Oncology NPGi. Chronic myelogenous leukemia:
National Comprehensive Cancer Network; 2008 Available from URL:
nccn.org/professionals/physician_gls/PDF/cml.pdf 4. Baccarani M, Saglio G, Goldman J, et al:
Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert
panel on behalf of the European Leukemia Net. Blood 2006;108:1809-1820 5. Jones D, Kamel-Reid S,
Bahler D, et al: Laboratory practice guidelines for detecting and reporting BCR-ABL drug resistance
mutations in chronic myelogenous leukemia and acute lymphoblastic leukemia A Report of the
Association for Molecular Pathology. J Mol Diagn 2009;11:4-11
Bean Black IgE
Interpretation: Conventional RAST Scoring Guide Class IgE (kU/L Comment 0 or = 17.5 Strong Positive
Reference Values:
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