Distinct bone marrow morphologic features discriminate myelodysplastic syndromes patients with and without an early platelet response to decitabine

Absence of early platelet increment in healthy mice during decitabine treatment

“…3 c). As published earlier, biopsies of MDS patients with EPR after DAC treatment displayed an increased number of “naked” MKs with a large nucleus and less cytoplasm indicating high rates of platelet shedding 13 . Therefore, we stained bone marrow cryosections for GPIX (MK and platelet specific marker) and found no alteration in the percentage of “naked” MKs in DAC-treated mice compared to control mice (Fig.…”

“…Additional studies will be needed using mouse models, which are engineered to recapitulate MDS characteristics. Interestingly, patients with EPR showed an overall stable or even increased bone marrow cellularity after DAC treatment, whereas non-responsers showed reduced cellularity 13 . In agreement with the patient data, we observed reduced bone marrow cellularity in mice after DAC treatment.…”

“…The mechanism of how DAC increases the platelet count has remained elusive. The analysis of MK morphology in bone marrow biopsies of MDS patients with EPR after DAC treatment showed that a larger pool of MKs potentially underwent platelet shedding as more “naked” MKs were observed 13 . Another study showed a 30% platelet count increase in Balb/c mice 12 h after 15 mg/m 2 i.v.…”

“…Data from in vitro studies suggested enhanced megakaryocyte (MK) maturation and platelet release to be responsible for the increased platelet count in mice and human patients 11 , 12 . Recently, the analysis of bone marrow biopsies of MDS patients with EPR revealed more juvenile MKs before DAC treatment and more naked MKs, indicative for platelet shedding, after DAC treatment 13 . To better understand the impact of DAC on bone marrow MKs and the bone marrow compartment in vivo, we treated mice with DAC and examined bone marrow sections.…”