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Gene expression data from children diagnosed with ALL in vitro sensitive or resistant to prednisolone


ABSTRACT: Although the prognosis for childhood Acute Lymphoblastic Leukemia (ALL) in general has improved tremendously over the last decades, the survival chances for infants (<1 year of age) with ALL remains poor. A major obstacle hampering successful treatment results in infant ALL is cellular resistance to several drugs currently used in the treatment of ALL, especially to prednisolone (or prednisone). Therefore we set out to search for genes differentially expressed between from infant (children <1 year of age) and non-infant (children >1 year of age) ALL samples either resistant or sensitive to prednisolone. The in vitro prednisolone response in primary infant and non-infant ALL samples was determined by 4-day cytotoxicity (MTT) assays. Patient samples were characterized as either sensitive or resistant based on the LC50 value (i.e. the concentration of prednisolone lethal to 50% of the leukemic cells). Prednisolone sensitivity was defined by LC50 values <0.1 ug/mL prednisolone, and prednisolone resistance by LC50 values >150 ug/mL. Samples showing intermediate in vitro prednisolone responses were excluded. In total 25 infant (<1 year of age) and 27 non-infant (>1 year of age) ALL samples were selected for RNA extraction and hybridization on Affymetrix HU133A microarrays. The obtained gene expression signatures were used to identify gene differentially expressed between prednisolone resistant and sensitive patients, in order to gain insights into the mechanism(s) underlying prednisolone resistance in infant and non-infant ALL.

ORGANISM(S): Homo sapiens

SUBMITTER: Ronald Stam 

PROVIDER: E-GEOD-19143 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Association of high-level MCL-1 expression with in vitro and in vivo prednisone resistance in MLL-rearranged infant acute lymphoblastic leukemia.

Stam Ronald W RW   Den Boer Monique L ML   Schneider Pauline P   de Boer Jasper J   Hagelstein Jill J   Valsecchi Maria G MG   de Lorenzo Paola P   Sallan Stephen E SE   Brady Hugh J M HJ   Armstrong Scott A SA   Pieters Rob R  

Blood 20091204 5


MLL-rearranged acute lymphoblastic leukemia (ALL) represents an unfavorable type of leukemia that often is highly resistant to glucocorticoids such as prednisone and dexamethasone. Because response to prednisone largely determines clinical outcome of pediatric patients with ALL, overcoming resistance to this drug may be an important step toward improving prognosis. Here, we show how gene expression profiling identifies high-level MCL-1 expression to be associated with prednisolone resistance in  ...[more]

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