MPL expression is predictive of cytopenia in a multicenter AML cohort. (A) Peripheral blood counts are shown as a function of bone marrow blast count in patients with newly diagnosed AML/refractory anemia with excess blasts from the Dutch-Swiss-Belgian HOVON study group (validation cohort) (N = 437). Pearson product-moment correlation coefficient is stated. (B) Gene set enrichment analysis of the BIOCARTA_TPO_PATHWAY gene set (supplemental Table 3) in AML patients with severe thrombocytopenia (0-20 G/L) at diagnosis compared with patients with platelet counts between 50 and 100 G/L (average in AML, 79 G/L) (N = 100). Enrichment score (ES), 0.56; significant at P < 5%. Arrow marks MPL at position 27 in ranked gene list. (C) Peripheral blood counts at diagnosis are shown as a function of MPL status by microarray. P < .0001 (platelet count), P = .0077 (ANC). (D) MPL mean expression as a function of AML (cytogenetic or molecular) subgroup according to the WHO 2008 classification. One-way ANOVA, P < .0001. (E) Initial peripheral blood counts in patients with AML with t(8;21) from both cohorts (N = 32) compared with all other AML patients. P < .0001 (platelet count, ANC). (F) Cartoon depicting the proposed mechanism leading to cytopenia in MPL^hi AML (right), contrasted with MPL^lo AML (left).