12. Targeted therapy: a possibility for the future?

Next-generation sequencing (NGS) and mutational analysis have uncovered significant insights into the pathogenicity of leukemia. Consequently, the chances to develop targeted therapies for leukemia have become a distinct possibility. However, due to misdiagnosis and paucity of clinical samples, such comprehensive analysis for MS is still lacking. Nonetheless, studies conducted with small cohorts of patients did report mutations in genes such as FLT3 and NPM1. Li et al. performed an NGS analysis with six patients with a custom panel targeting 21 common genes associated with AML and myelodysplastic syndrome (MDS) [44]. In addition to FLT3 and NPM1, the authors were also able to identify mutations in several genes such as KIT, TET2, EZH2, SF3B1 and ASXL1 akin to AML [44]. This report does provide substantial evidence of an underlying similarity in the pathogenicity between MS and AML. The importance of targeted therapy is further accentuated by Piccaluga and colleagues [45]. In this study, the authors used an anti-CD33 monoclonal antibody to treat MS patients with concurrent CD33-positive AML. Two out five patients in the study elicited a complete remission of both MS and AML, while two patients showed reductions of extramedullary disease only [45]. In a different study, treatment of MS patients with BCR-ABL1, FLT3-ITD and FIP1L1-PDGFRA mutations by tyrosine kinase inhibitors (TKIs) also showed encouraging outcome [46].

cytogenetic and chromosomal abnormalities. Also, bone marrow biopsy should be that part of the diagnosis. In fact, all isolated MS cases should be prophylactically treated for AML even if there is no detectable leukemia. Caution should be exercised when analyzing immunohistochemistry for MS. For example, CD43 and CD68, although, a reliable indicator of AML, should be correlated with CD33, myeloperoxidase staining for accurate MS diagnosis. Treatment should involve systemic chemotherapy as the first line of treatment with radiotherapy and allo-HCT as part of the consolidation therapy. Surgery should be employed for tumor resec-

Myeloid Sarcoma: The Other Side of Acute Leukemia http://dx.doi.org/10.5772/intechopen.74931 123

We need more prospective studies with larger patient cohorts to understand the mechanism(s) of MS development. In addition, future studies should be directed to whole genome sequencing of MS samples to understand the different genetic abnormalities associated with MS and how they differ from the corresponding bone marrow disease. Genetic information will also help in better patient stratification. As evident from the whole-body PET/CT imaging, the incidence of MS is more prevalent than expected indicating that we most likely have

Bone Marrow Trans and Cell Therapy, St Jude Children's Research Hospital, Memphis,

options. Therapeutic Advances in Hematology. 2011;2(5):309-316

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tion, if possible.

Author details

Bhaskar Kahali

United States

References

631-637

2009;114(14):3008-3017

Blood. 2011;118:3785-3793

underestimated the impact and implications of MS.

Address all correspondence to: bhaskar.kahali@stjude.org

Taken together these observations does suggest that akin to AML a similar sequencing (whole genome, whole exome, and RNA seq.) base analysis should be employed in case of MS. However, the success of such an endeavor depends on the obtainability of large cohorts of samples, which unfortunately is a rarity in case of MS. Large multicenter collaboration is essential to circumvent this problem.
