The immunological role of megakaryocytes is not well known. This project studies the involvement of megakaryocytes on immuno-inflammatory processes and the possible mechanism via the adhesion molecule CD36 and the synthesis of relevant cytokines. The expression of adhesion protein CD36 on human platelets, megakaryocytes and megakaryocytic cell lines (Meg-01, Dami, CHRF-288-11 and M-07e) was analyzed by using flow cytometry, ELISA and immunocytochemical methods. The expression of interleukin-1 (IL-1) to interleukin-10 (IL-10), TNF-alpha, TNF-gamma and IFN-gamma on the four megakaryocytic cell lines was also determined by RT-PCR. The effect of IL-1beta, IL-3, IL-6 and TPO on murine megakaryocyte colony formation (CFU-MK) was studied by using a plasma clot culture system. The CFU-MK was confirmed by acetylcholine esterase staining. The results showed that: (1) CD36 was expressed on platelets, megakaryocytes and the four megakaryocytic cell lines, the relative expression level is as follows: platelets > megakaryocytes > Meg-01 > Dami > CHRF-288-11 > M-07e, suggesting that the level of CD36 expression correlates with the degree of maturity of megakaryocytic differentiation; (2) inflammatory cytokines TNF-alpha, IL-1beta, IL-3 and IL-6 were detected in all the four megakaryocytic cell lines, suggesting that different stages of megakaryocytes can be as a source of inflammatory cytokines; and (3) IL-1beta, IL-3 and IL-6, as well as TPO, play a stimulating effect on CFU-MK formation, suggesting that there is an "autocrine" effect on megakaryocytopoiesis. The data obtained suggest that megakaryocytes may involve in immuno-inflammatory processes via the synthesis of platelet adhesion molecules and inflammatory cytokines.

BACKGROUNDChildhood cancer survivors were at risk of development of second malignant neoplasms. The aim of this study is to evaluate the incidence, risk factors and outcome of second malignant neoplasms in childhood cancer survivors in a tertiary paediatric oncology centre in Hong Kong, China.

METHODSWe performed a retrospective review of patients with childhood cancer treated in Children's Cancer Centre in Prince of Wales Hospital, Hong Kong, China between May 1984 and June 2009. Case records of patients who developed second malignant neoplasms were reviewed.

RESULTSTotally 1374 new cases aged less than 21-year old were treated in our centre in this 25-year study period. Twelve cases developed second malignant neoplasms with 10-year and 20-year cumulative incidence of 1.3% (95% confidence interval 0.3% - 2.3%) and 2.9% (95% confidence interval 1.1% - 4.7%) respectively. Another 4 cases were referred to us from other centres for the management of second malignant neoplasms. In this cohort of 16 children with second malignant neoplasms, the most frequent second malignant neoplasms were acute leukemia or myelodysplastic syndrome (n = 6) and central nervous system tumor (n = 4). Median interval between diagnosis of primary and second malignant neoplasms was 7.4 years (range 2.1 - 13.3 years). Eight patients developed second solid tumor within the previous irradiated field. Radiotherapy significantly increased the risk of development of second solid tumor in patients with acute lymphoblastic leukemia (P = 0.027). Seven out of 16 patients who developed second malignant neoplasms had a family history of cancer among the first or second-degree relatives. Nine patients died of progression of second malignant neoplasms, mainly resulted from second central nervous system tumor and osteosarcoma.

CONCLUSIONSCumulative incidence of second cancer in our centre was comparable to western countries. Radiotherapy was associated with second solid tumour among patients with acute lymphoblastic leukemia. Patients who developed second brain tumor and osteosarcoma had a poor outcome.

Adolescent ; Adult ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Hong Kong ; epidemiology ; Humans ; Infant ; Infant, Newborn ; Male ; Neoplasms ; epidemiology ; Neoplasms, Second Primary ; epidemiology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Retrospective Studies ; Survivors ; statistics & numerical data ; Young Adult