Author details

Bhaskar Kahali

12. Targeted therapy: a possibility for the future?

122 Hematology - Latest Research and Clinical Advances

essential to circumvent this problem.

13. Conclusion

bone marrow.

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].

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

Myeloid sarcoma is acknowledged as a separate disease entity for a significant period. It is an extremely rare hematological malignancy and is often associated with poor prognosis. Due to the scarcity of samples, there is no risk assessment study for MS. There are several unanswered questions for MS. Specifically, is there a bias for certain AML (such as CBF leukemia) to induce extramedullary infiltration. If yes, what is the primary mechanism(s) that drives the processes? Does MS represent alternate molecular landscapes, clonal evolution, from the original bone marrow disease? It can be argued that MS reflects a state of reduced immune surveillance in a patient at diagnosis or following hematopoietic stem cell transplantation. Consequently, this raises the possibility that MS may serve as a sanctuary site for leukemic relapse. The observation supports this implication that isolated MS ultimately gives rise to leukemia involving

MS is often challenging to identify and even more challenging to diagnose. Owing to its similarity with solid tumors, MS is often misdiagnosed, particularly as non-Hodgkin lymphoma. Accurate diagnosis of MS required an orchestrated approach involving whole body imaging (PET/CT, MRI), broad panels of immunohistochemical staining, and FISH assay for Address all correspondence to: bhaskar.kahali@stjude.org

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