HCP need to improve their knowledge of TCAM and facilitate open communication about TCAM with families so parents feel safe to discuss their interest in it.

Gemtuzumab ozogamicin, an anti-tumour antibiotic linked to an anti-CD33 antibody (Mylotarg®), has been well studied in AML in adults but to a lesser extent in children. No review has yet been published on the dose-related toxicity and efficacy of gemtuzumab ozogamicin in pediatric AML patients. Here we looked at 14 studies then scatterplots and linear regressions were used to estimate the relationship between the dose of gemtuzumab and its toxicity and efficacy. A nonsignificant increase in bilirubin level and in incidence of veno-occlusive disease was seen with higher doses of gemtuzumab ozogamicin when used as single-agent. In terms of efficacy, even a low dose of 3 mg/m 2 of gemtuzumab ozogamicin can have antileukemic effect, but available data do not allow conclusions on its dose-dependency. Data indicate that higher doses of gemtuzumab ozogamicin account for more adverse events. The data do not show that a high dose is required for anti-leukemic efficacy of gemtuzumab ozogamicin. This study also indicates that there seems to be a role for gemtuzumab ozogamicin in the treatment of pediatric AML and further studies are required to assess its optimal dose, schedule and balance between efficacy and side-effects. ARTICLE HISTORY

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It has been well established that dysregulated activation of kinases is essential for the development of acute myeloid leukemia (AML). In contrast, little is known about the role of their dephosphorylation counterparts, the tyrosine phosphatases. Here we performed whole tyrosine phosphatome sequencing in 15 pediatric AML samples and found a somatic P394L mutation in the FERM-adjacent region of PTPN4. In the absence of a crystal structure of PTPN4, bioinformatics analysis with the software tool PROVEAN (Protein Variation Effect Analyzer) revealed that this P394L mutation is expected to inflict a deleterious effect on the phosphatase activity of PTNP4. Exploring the frequency of this PTPN4 mutation in 227 acute leukemia samples uncovered an additional silent A364A mutation in exon 13 of PTPN4. No additional mutations were found, which further emphasizes the low mutation burden in pediatric AML. Further functional studies are warranted to explore the actual impact of this P394L mutation on the structure and/or function of PTPN4.