Mutations in NPM1 can be used for minimal residual disease (MRD) analysis in acute myeloid leukemia (AML). We here applied a newly introduced method, deep sequencing, allowing for simultaneous analysis of all recurrent NPM1 insertions and thus constituting an attractive alternative to multiple PCRs for the clinical laboratory. We retrospectively used deep sequencing for measurement of MRD pre- and post-allogeneic hematopoietic stem cell transplantation (alloHCT). For 29 patients in morphological remission at the time of alloHCT, the effect of deep sequencing MRD on outcome was assessed. MRD positivity was defined as variant allele frequency ≥0.02%. Post-transplant MRD status was significantly and independently associated with clinical outcome; 3-year relapse-free survival 20% vs 85% (p < .001), HR 45 (95% CI 2-1260), and overall survival 20% vs 89% (p < .001), HR 49 (95% CI 2-1253). Thus, the new methodology deep sequencing is an applicable and predictive tool for MRD assessment in AML.
CME Accreditation Statement: This activity ("JMD 2019 CME Program in Molecular Diagnostics") has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of the American Society for Clinical Pathology (ASCP) and the American Society for Investigative Pathology (ASIP). ASCP is accredited by the ACCME to provide continuing medical education for physicians. The ASCP designates this journal-based CME activity ("JMD 2019 CME Program in Molecular Diagnostics") for a maximum of 18.0 AMA PRA Category 1 Credit(s) ä. Physicians should claim only credit commensurate with the extent of their participation in the activity.
Micro-ribonucleic acid-155 (miR-155) is one of the first described oncogenic miRNAs. Although multiple direct targets of miR-155 have been identified, it is not clear how it contributes to the pathogenesis of acute myeloid leukemia. We found miR-155 to be a direct target of Meis1 in murine Hoxa9/Meis1 induced acute myeloid leukemia. The additional overexpression of miR-155 accelerated the formation of acute myeloid leukemia in Hoxa9 as well as in Hoxa9/Meis1 cells in vivo. However, in the absence or following the removal of miR-155, leukemia onset and progression were unaffected. Although miR-155 accelerated growth and homing in addition to impairing differentiation, our data underscore the pathophysiological relevance of miR-155 as an accelerator rather than a driver of leukemogenesis. This further highlights the complexity of the oncogenic program of Meis1 to compensate for the loss of a potent oncogene such as miR-155. These findings are highly relevant to current and developing approaches for targeting miR-155 in acute myeloid leukemia.
BackgroundA primary goal for the development of EHRs and EHR-related technologies should be to facilitate greater knowledge management for improving individual and community health outcomes associated with HIV / AIDS. Most of the current developments of EHR have focused on providing data for research, patient care and prioritization of healthcare provider resources in other areas. More attention should be paid to using information from EHRs to assist local, state, national, and international entities engaged in HIV / AIDS care, research and prevention strategies. Unfortunately the technology and standards for HIV-specific reporting modules are still being developed.Methods:A literature search and review supplemented by the author’s own experiences with electronic health records and HIV / AIDS prevention strategies will be used. This data was used to identify both opportunities and challenges for improving public health informatics primarily through the use of latest innovations in EHRs. Qualitative analysis and suggestions are offered for how EHRs can support knowledge management and prevention strategies associated with HIV infection.Results:EHR information, including demographics, medical history, medication and allergies, immunization status, and other vital statistics can help public health practitioners to more quickly identify at-risk populations or environments; allocate scarce resources in the most efficient way; share information about successful, evidenced-based prevention strategies; and increase longevity and quality of life.Conclusion:Local, state, and federal entities need to work more collaboratively with NGOs, community-based organizations, and the private sector to eliminate barriers to implementation including cost, interoperability, accessibility, and information security.
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