Possible implications for choice of MRD method, timing of MRD monitoring, and guidance of therapy are discussed in general and in some detail for certain types of leukemia with specific molecular markers to monitor, including core binding factor (CBF)-leukemias and NPM1-mutated leukemias.
Our results indicate that INPP4B promotes leukemia cell survival via SGK3 activation, and INPP4B might be a potential target in the treatment of NPM1-mutated AML.
However, miR-10a/b overexpression was not associated with complete remission rate, and did not have an impact on both leukemia free survival and overall survival time in non-M3 AML patients without NPM1 mutation.
By analyzing the enrichment of differentially‑expressed genes in chemical and genetic perturbation datasets, it was found that genes, which were upregulated in the FLT3 high expression group had myeloid lymphoid leukemia‑ and nucleophosmin 1‑like signatures, indicating that the overexpression of FLT3 may use the same mechanism to promote leukemia.
Areas covered: Available techniques include multi-color flow cytometry (MFC) of leukemia associated immunophenotypes (LAIP), quantitative reverse transcriptase polymerase chain reaction (QRT-PCR) for detecting fusion and mutated genes (RUNX1-RUNX1T1, CBFB-MYH11, and NPM1), overexpression of genes such as WT1, and next generation sequencing (NGS) for MRD.
We conclude that although actD does not increase NPM concentration in the cytoplasm, it could improve the effect of standard chemotherapy in leukemias through more general mechanisms.
NPM mutations are the most common genetic change in patients with acute leukemia (AML); therefore, our model may be applicable to other more common leukemias driven by NPM.
We evaluated leukemia-associated immunophenotypes (LAIP) and their correlation with fms-like tyrosine kinase 3 (FLT3) and nucleophosmin (NPM1) gene mutational status in order to contribute a better identification of patients at highest risk of relapse in acute myeloid leukemia (AML).
This may be individually combined with multiparameter flow cytometry (MFC) for the detection of residual cells with a leukaemia phenotype and quantitative real-time polymerase chain reaction (RQ-PCR) to assess gene expression, e.g., of WT1 or the residual mutation load (e.g., in case of an NPM1 mutation).
Our findings suggest that while K-RAS mutations are infrequent in CN-AML, activating K-RAS mutations may cooperate with mutated NPM1 to induce leukemia.
In this review, we focus on the leukemia-associated NPM1 C-terminal domain and describe its structure, function, and the effect exerted by leukemic mutations.