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may be more effi cacious. Furthermore, TK inhibitor-mediated molecular response
provides valuable risk stratifi cation and prognostic information on long-term out-
comes. Despite these attributes, informed, universal, practical utilization of this
well-established monitoring test will require heightened efforts by the molecular
diagnostics laboratory community to adopt the standardized reporting units of the
International Scale. Without widespread adoption of the International Scale, the
consensus major molecular response and early molecular response treatment thresh-
olds will not be defi nable, and optimal clinical outcomes for patients with CML
may not be achieved (Press et al. 2013 ).
Personalized Management of Multiple Myeloma
Multiple myeloma (MM), the second most common hematological cancer after
non-Hodgkin’s lymphoma, is considered incurable although some patients survive
for a number of years following diagnosis. About 50,000 people in the US are living
with the disease, and an estimated 16,000 new cases are diagnosed annually. Despite
improvements in therapy, the 5-year survival rate in multiple myeloma is only 32 %
and durable responses are rare. Multiple myeloma is a neoplasia of clonally
expanded malignant bone marrow plasma cells. Previously two genetic subtypes of
myeloma were known: (1) hyperdiploid MM characterized by extra copies of entire
chromosomes and patients with this subtype appear to fare better; (2) non-
hyperdiploid form lacks these extra chromosomes and instead has abnormal rear-
rangements between different chromosomes with worse outlook for the patients
with this subtype. The roles played by various abnormalities in the initiation and
progression of myeloma are only beginning to be understood, but it been observed
that different abnormalities vary from one patient to the other.
Pharmacogenomic studies in multiple myeloma are helping to set the stage for
individualized therapy. Although relatively few in numbers, these studies are already
providing new therapeutic targets and avenues for drug discoveries as well as con-
tributing to novel prognostic markers in multiple myeloma. Genetics and gene
expression profi ling technology have improved molecular-based patient stratifi ca-
tion and prognostic staging, expanded knowledge of the molecular mechanism of
chemotherapeutic agents, and provided a better understanding of multiple myeloma.
Distinct genetic subtypes of MM have different prognoses and might be treated
most effectively with drugs specifi cally targeted to those subtypes. For further
analysis of many DNA alterations in the MM genome, an algorithm has been cre-
ated based on a computational method, which is used to group the results in a way
that yield distinctive genomic features from the CGH data. Four distinct myeloma
subtypes based on genetic patterns emerge from these data of which two corre-
spond to the non-hyperdiploid and hyperdiploid types; the latter contains two fur-
ther subdivisions, called k1 and k2. Those with the k1 pattern have a longer survival
than those with k2. These results defi ne new disease subgroups of MM that can be
correlated with different clinical outcomes. The fi ndings pave the way for treat-
10 Personalized Therapy of Cancer