The isoforms of c-MPL plays an instrumental role in regulating the severity of leukemic conditions

Background: Acute myeloid leukemia (AML) is a hematopoietic defect and various clinical studies confirms that the development of this condition has a correlation with the hematopoietic receptor c-MPL. The function of MPL is mostly regulated by the crosstalk and stoichiometry of the different isoforms of c-MPL. Though expression of c-MPL in AML cases are studied, the regulation of the isoforms, their balance and mechanism of action in conditions like AML needs to be revealed, to develop c-MPL as a therapeutic target for AML cases. Through this work we have reconfirmed that c-MPL expression increases in AML, but the severity of the condition is independent of the total MPL expression. Methods: Molecular techniques like qRT-PCR, western blotting, immunophenotyping, and immunofluorescence were used to investigate the expression of c-MPL isoforms and their correlation with AML severity. The significance of the work depends on the statistical analysis of the experimental and technical triplicates. Conclusion: We have confirmed that the severity of the AML condition directly depends on the expression of MPL-FL isoform, more precisely, on the increase in the ration of MPL-FL/MPL-TR. Furthermore, we have observed that with increase in MPL-FL isoforms, inactive STAT5 converts to active pSTAT5 to promote the transition of HSC G0 state to HSC proliferative state to bring in the severity. Interpretation: Our study provides compelling evidence to establish the regulatory role of c-MPL isoforms, particularly MPL-FL in bringing in severity in AML conditions. This finding is a significant step towards developing c-MPL as a therapeutic target for AML cases.