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Treatment with forskolin arrests proliferation; induces cell death; represses the expression of\n                      <jats:italic>MYC<\/jats:italic>\n                      ,\n                      <jats:italic>HOXA9<\/jats:italic>\n                      and\n                      <jats:italic>HOXA10<\/jats:italic>\n                      ; stimulates PP2A activity; and attenuates the activity of ERK1\/2 in\n                      <jats:italic>KMT2A<\/jats:italic>\n                      \u2010r AML cells. Forskolin increases sensitivity to standard\u2010of\u2010care daunorubicin in\n                      <jats:italic>KMT2A<\/jats:italic>\n                      \u2010AML cell lines and PDX. Silencing\n                      <jats:italic>PPP2CA<\/jats:italic>\n                      partially rescues the cytotoxic effect of forskolin, stimulates ERK1\/2, inhibits GSK3\u03b2, and abolishes the forskolin\u2010mediated repression of c\u2010\n                      <jats:italic>MYC<\/jats:italic>\n                      and\n                      <jats:italic>HOXA10,<\/jats:italic>\n                      but it did not affect the potentiation of response to daunorubicin. This effect was also not dependent on increase of cAMP, but it was because of increase in the intracellular accumulation of daunorubicin, through inhibition of drug efflux pump P\u2010glycoprotein 1 (multidrug resistance protein).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>\n                      In conclusion, our findings highlight a novel mechanism of action for forskolin and support a potential role of this natural compound in combination with current conventional agent daunorubicin in the treatment of\n                      <jats:italic>KMT2A<\/jats:italic>\n                      \u2010r AML.\n                    <\/jats:p>\n                  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