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Personalized Management of Myelodysplastic Syndrome
Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders of
ineffective hematopoiesis that characteristically demonstrate peripheral blood cyto-
penia, bone marrow hypercellularity, and morphologically defi ned dysplasia of one
or more hematopoietic lineages. Classical metaphase cytogenetics and judicious use
of FISH play central roles in the contemporary diagnosis and classifi cation of
MDS. An abundance of recent molecular studies are beginning to delineate addi-
tional genetic and epigenetic aberrations associated with these disorders, which
affect diagnosis, prognosis, and therapy. Classifi cation systems are evolving from a
primarily hematological and morphological basis toward a multifactorial apprecia-
tion that includes histomorphology, metaphase cytogenetics, and directed molecular
studies. Rapidly growing understanding of the genetic basis of MDS holds much
promise for testing, and a frame of reference has been provided for discussion of
current testing protocols and for addressing testing modalities likely to enter clinical
practice in the near future (Nybakken and Bagg 2014 ).
Cytogenetic analyses are mandatory for risk stratifi cation and for monitoring
response to drug treatment in MDS. Low-dose demethylating agents such as 5-aza-
2 ′-deoxycytidine (decitabine) and 5-azacytidine (azacitidine, Vidaza) have been
explored for the treatment of MDS with the aim to revert a methylator phenotype.
Decitabine treatment is associated with a response rate that is higher in patients with
high-risk cytogenetics (i.e., complex karyotype and/or abnormalities of chromo-
some 7) than in patients with intermediate-risk cytogenetics (two abnormalities or
single abnormalities excluding 5q-, 20q-, and -Y). Following decitabine treatment
of patients with abnormal karyotype, approximately one-third achieve a major cyto-
genetic response that can be confi rmed by FISH analyses, while in two-thirds of
patients, the abnormal karyotype persists but hematologic improvement may be
observed during continued treatment. The most frequently studied gene in myelo-
dysplasia is the cell cycle regulator p15. Hypermethylation of p15 in MDS is
reversed during treatment with decitabine, resulting in reactivation of this gene.
Somatic mutations in MDS may infl uence the clinical phenotype but are not
included in current prognostic scoring systems. Combination of genomic approaches,
including NGS and MS-based genotyping, identifi ed somatic mutations in 18 genes
in samples of bone marrow aspirate from patients with MDS and associated them
with specifi c clinical features (Bejar et al. 2011 ). Mutations in TP53, EZH2, ETV6,
RUNX1, and ASXL1 were found to be predictors of poor overall survival in MDS
patients independently of established risk factors.
Personalized Management of Lymphomas
Personalized Management B Cell Lymphomas
B cell lymphomas are tumors of cells of the immune system that include Hodgkin’s
and non-Hodgkin’s lymphomas such as follicular lymphoma. B cells are the immune
system cells that produce antibodies. Genetic aberrations can cause B cells to
10 Personalized Therapy of Cancer