Myeloid leukemia of Down syndrome (ML-DS) is characterized by a distinct natural history and is classified by the World Health Organization (WHO) as an independent entity, occurring with unique clinical and molecular features. The presence of a long preleukemic, myelodysplastic phase, called transient abnormal myelopoiesis (TAM), precedes the initiation of ML-DS and is defined by unusual chromosomal findings. Individuals with constitutional trisomy 21 have a profound dosage imbalance in the hematopoiesis-governing genes located on chromosome 21 and thus are subject to impaired fetal as well as to neonatal erythro-megakaryopoiesis. Almost all neonates with DS develop quantitative and morphological hematological abnormalities, yet still only 5–10% of them present with one of the preleukemic or leukemic conditions of DS. The acquired mutations in the key hematopoietic transcription factor gene GATA1, found solely in cells trisomic for chromosome 21, are considered to be the essential step for the selective growth advantage of leukemic cells. While the majority of cases of TAM remain clinically ‘silent’ or undergo spontaneous remission, the remaining 20% to 30% of them progress into ML-DS until the age of 4 years. The hypersensitivity of ML-DS blasts to chemotherapeutic agents, including but not limited to cytarabine, and drugs’ increased infectious and cardiac toxicity have necessitated the development of risk-adapted treatment protocols for children with ML-DS. Recent advances in cytogenetics and specific molecular mechanisms involved in the evolution of TAM and ML-DS are reviewed here, as well as their integration in the improvement of risk stratification and targeted management of ML-DS.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by isolated thrombocytopenia. It is diagnosed in patients with a platelet count below 100,000 per cubic millimeter in whom other causes of thrombocytopenia have been ruled out, and its diagnosis is generally one of exclusion. Clinical manifestations of patients may vary from asymptomatic disease to mild mucocutaneous or life-threatening bleeding. Glucocorticoids are used as first-line treatment for ITP, while other second-line medications, mainly thrombopoietin-receptor agonists (TPO-RA) and rituximab, are given to patients in whom ITP does not remit, or relapses soon after glucocorticoid treatment. Refractoriness of ITP strongly questions its diagnosis and necessitates a thorough clinical and laboratory work-up to decide whether that is the case of refractory ITP or a misdiagnosis. The aim of this review is to summarize the conditions associated with isolated thrombocytopenia and highlight the characteristics of confusing cases. Even though the case of a myelodysplastic syndrome presented with isolated thrombocytopenia (MDS-IT) is relatively rare and not well-established in the literature, it constitutes one of the most predominant misdiagnoses of refractory ITP. MDS-IT patients are thought to present with multilineage dysplasia, normal karyotype and low risk prognostic score, based on IPSS-R. It has been shown that a significant proportion of MDS-IT patients are misdiagnosed as having the more common ITP. Therefore, it is crucial that in confusing cases of persistent thrombocytopenia a detailed diagnostic work-up is applied—including evaluation of peripheral-blood smear, bone marrow examination and cytogenetic testing—to avoid unnecessary therapy delay.