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Myeloid leukaemia of Down syndrome (ML‐DS) is an acute megakaryoblastic/erythroid leukaemia uniquely found in children with Down syndrome (constitutive trisomy 21). It has a unique clinical course, being preceded by a pre‐leukaemic condition known as transient abnormal myelopoiesis (TAM), and provides an excellent model to study multistep leukaemogenesis. Both TAM and ML‐DS blasts carry acquired N‐terminal truncating mutations in the erythro‐megakaryocytic transcription factor GATA1. These result in exclusive production of a shorter isoform (GATA1s). The majority of TAM cases resolve spontaneously without the need for treatment; however, around 10% acquire additional cooperating mutations and transform to leukaemia, with differentiation block and clinically significant cytopenias. Transformation is driven by the acquisition of additional mutation(s), which cooperate with GATA1s to perturb normal haematopoiesis. [ABSTRACT FROM AUTHOR]

Summary Context The optimal duration of dopamine agonist (DA) therapy in prolactinoma is unknown. There are concerns that despite low recurrence rates in highly selected groups, high recurrence rates after DA withdrawal may occur in routine practice. Objective To explore recurrence of hyperprolactinaemia and predictive factors following DA withdrawal in patients with microprolactinoma and macroprolactinoma. Design A retrospective study on adult patients with confirmed prolactinoma attending the Oxford Endocrine Department. Patients and Measurements We identified patients with macroprolactinoma ( n = 15) and microprolactinoma ( n = 45) treated with DA therapy for >3 years, with a trial off DA therapy. None had other treatments. Measurements included recurrence of hyperprolactinaemia following DA withdrawal, tumour size (macroprolactinomas), duration of DA therapy, prolactin levels (baseline, during DA therapy, recurrence) and time to recurrence. Data were reported as mean (range). Results During DA therapy, prolactin levels suppressed to normal range in all patients with macroprolactinoma and microprolactinoma, and most macroprolactinomas ( n = 14) had substantial tumour shrinkage. Hyperprolactinaemia recurred in 93% of macroprolactinomas ( n = 14) at 8·8 months (3-36) and 64% of microprolactinomas ( n = 29) at 4·8 months (3-12). Duration of DA therapy was 7·5 years (4-15) for macroprolactinomas and 4·1 years (3-10) for microprolactinomas. Prolactin levels during DA therapy were 144 mU/l (7-336) for macroprolactinomas and 278 mU/l (30-629) for microprolactinomas. For microprolactinomas, prolactin levels during DA therapy were less suppressed in those with recurrence than in those without recurrence ( P < 0·05). Conclusions In routine practice, hyperprolactinaemia recurs early in most macroprolactinomas (93%) and microprolactinomas (64%) following DA therapy discontinuation. For most macroprolactinomas, cessation of DA cannot be recommended even after 7 years of therapy. [ABSTRACT FROM AUTHOR]