Block of C/EBPα function by phosphorylation in acute myeloid leukemia with FLT3 activating mutations

Mutations constitutively activating FLT3 kinase are detected in ∼30% of acute myelogenous leukemia (AML) patients and affect downstream pathways such as extracellular signal–regulated kinase (ERK)1/2. We found that activation of FLT3 in human AML inhibits CCAAT/enhancer binding protein α (C/EBPα) function by ERK1/2-mediated phosphorylation, which may explain the differentiation block of leukemic blasts. In MV4;11 cells, pharmacological inhibition of either FLT3 or MEK1 leads to granulocytic differentiation. Differentiation of MV4;11 cells was also observed when C/EBPα mutated at serine 21 to alanine (S21A) was stably expressed. In contrast, there was no effect when serine 21 was mutated to aspartate (S21D), which mimics phosphorylation of C/EBPα. Thus, our results suggest that therapies targeting the MEK/ERK cascade or development of protein therapies based on transduction of constitutively active C/EBPα may prove effective in treatment of FLT3 mutant leukemias resistant to the FLT3 inhibitor therapies

Users' perceptions of the need for cash flow statements — Australian evidence

Professional accounting bodies have endorsed claims of the need for cash flow information through their issuance of Standards on cash flow statements. Few empirical studies have tested the extent to which decision-makers actually use cash flow information. Whilst market-based studies have tested the reaction of the stock market to the release of cash flow information, they have not established the usefulness of cash flow information to financial statement users. Such a study is important not just for the signals it gives to regulators, but also by virtue of the importance those signals have for the preparers of accounting information. The academic and professional literature, identify four possible contributing factors of demand for cash flow information: (i) the limitations of conventional accrual accounting, (ii) dissatisfaction with the funds statement, (iii) relevance for users' decisions, and (iv) changes in the reporting environment. To determine the extent to which investors and creditors agreed with these factors in favour of publishing cash flow data, a survey was conducted of workers in the finance industry in Australia. The results support the claims made in the academic and professional literature as to the need for cash flow information. Cash flow statements have become important sources of information for users. They have not, however, replaced the conventional income statement and balance sheet. All three financial statements are considered to be complementary.