Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of humans to investigate between transient vs acute megakaryoblastic leukaemia (TMD vs AMKL) in Downs syndrome

ABSTRACT: Comparison of transient myeloproliferative disorder and acute megakaryoblastic leukaemia in Down syndrome.

ORGANISM(S): Homo sapiens

DISEASE(S): Down syndrome, acute megakaryoblastic leukaemia

SUBMITTER: Gareth Denyer

PROVIDER: E-MEXP-72 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Microarray transcript profiling distinguishes the transient from the acute type of megakaryoblastic leukaemia (M7) in Down's syndrome, revealing PRAME as a specific discriminating marker.

McElwaine Suzanne S Mulligan Claire C Groet Jürgen J Spinelli Monica M Rinaldi Andrea A Denyer Gareth G Mensah Afua A Cavani Simona S Baldo Chiara C Dagna-Bricarelli Franca F Hann Ian I Basso Giuseppe G Cotter Finbarr E FE Nizetic Dean D

British journal of haematology 20040601 6

Transient myeloproliferative disorder (TMD) is a unique, spontaneously regressing neoplasia specific to Down's syndrome (DS), affecting up to 10% of DS neonates. In 20-30% of cases, it reoccurs as progressive acute megakaryoblastic leukaemia (AMKL) at 2-4 years of age. The TMD and AMKL blasts are morphologically and immuno-phenotypically identical, and have the same acquired mutations in GATA1. We performed transcript profiling of nine TMD patients comparing them with seven AMKL patients using A ...[more]

PMID: 15180862

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Project description:The cellular ontogeny of hematopoietic stem cells (HSCs) remains poorly understood because their isolation from and their identification in early developing small embryos are difficult. We attempted to dissect early developmental stages of HSCs using an in vitro mouse embryonic stem cell (ESC) differentiation system combined with inducible HOXB4 expression. Here we report the identification of pre-HSCs and an embryonic type of HSCs (embryonic HSCs) as intermediate cells between ESCs and HSCs. Both pre-HSCs and embryonic HSCs were isolated by their c-Kit+CD41+CD45- phenotype. Pre-HSCs did not engraft in irradiated adult mice. After co-culture with OP9 stromal cells and conditional expression of HOXB4, pre-HSCs gave rise to embryonic HSCs capable of engraftment and long-term reconstitution in irradiated adult mice. Blast colony assays revealed that most hemangioblast activity was detected apart from the pre-HSC population, implying the early divergence of pre-HSCs from hemangioblasts. Gene expression profiling suggests that a particular set of transcripts closely associated with adult HSCs is involved in the transition of pre-HSC to embryonic HSCs. Experimental strategy consisted of EB formation, co-culture with OP9 cells, and functional assays. iHOXB4 ESCs were allowed to differentiate spontaneously into EBs for 6 days without HOXB4 expression. We decided to fractionate EB6 cells mainly because by day 6 of culture the number of multipotent progenitors reaches a plateau and several surface markers become detectable. CD41 is known as a marker for the initiation of definitive hematopoiesis. CD41 appeared in a significant proportion of EB cells on day 6 of culture. Induced HOXB4 expression during EB formation did not affect the generation of colony forming cells and repopulating cells in the OP9 and iHOXB4 system or the appearance of surface markers in EB cells. EB6 cells were analyzed and sorted by flow cytometry. Sorted EB6 cells were co-cultured with OP9 cells for various days under HOXB4-on or -off conditions. The minimal requirement of the co-culture period appeared to be only 4 days, which is much shorter than previously thought. After a second analysis and fractionation by flow cytometry, cells were subjected to in vivo repopulating assays under HOXB4-on or -off conditions.

Dataset Information

Transcription profiling of humans to investigate between transient vs acute megakaryoblastic leukaemia (TMD vs AMKL) in Downs syndrome

Publications

Microarray transcript profiling distinguishes the transient from the acute type of megakaryoblastic leukaemia (M7) in Down's syndrome, revealing PRAME as a specific discriminating marker.

Similar Datasets

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