Blood
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Deficiency of the granulocyte-macrophage colony-stimulating factor (GM-CSF)/interleukin-3 (IL-3)/IL-5 receptors common beta chain (betac) is a cause of fatal respiratory failure. betac deficiency manifests as pulmonary alveolar proteinosis (PAP). PAP has heterogenous etiologies that may be genetic or aquired. Some cases of PAP have been reported to be associated with hematologic malignancies such as acute myeloid leukemia (AML). ⋯ The response to growth factors acting via a growth factor receptor distinct from the GM-CSF/IL-3/IL-5 system (recombinant human granulocyte colony-stimulating factor [rhG-CSF]) was normal. After antileukemic treatment, the pulmonary symptoms resolved and betac or betac plus GM-CSFR alpha expression was normal. Our findings provide evidence that a defect in the expression of betac or betac plus GM-CSFR alpha on AML blasts can be associated with respiratory failure in patients with AML.
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Comparative Study
Clinical significance of MLL-AF4 fusion transcript expression in the absence of a cytogenetically detectable t(4;11)(q21;q23) chromosomal translocation.
Leukemic cells from bone marrow (BM) of 17 infants and 127 children with newly diagnosed ALL, as well as fetal liver and BM and normal infant BM samples, were analyzed for presence of a t(4;11) translocation using standard cytogenetic techniques and expression of an MLL-AF4 fusion transcript using standard reverse transcriptase-polymerase chain reaction (RT-PCR) assays as well as nested RT-PCR that is 100-fold more sensitive than standard RT-PCR. Overall, 9 of 17 infants and 17 of 127 noninfant pediatric ALL patients were positive for expression of MLL-AF4 fusion transcripts, as determined by standard and/or nested RT-PCR assays. None of the MLL-AF4(+) cases were positive for E2A-PBX1 or BCR-ABL fusion transcript expression. ⋯ Infants with MLL-AF4(+) ALL had poor outcomes, whereas non-infant MLL-AF4(+)/t(4;11)- patients had favorable outcomes similar to MLL-AF4(-) patients. Notably, MLL-AF4 transcripts also were detected by nested RT-PCR in 4 of 16 fetal BMs, 5 of 13 fetal livers, and 1 of 6 normal infant BMs, but not in any of the 44 remission BM specimens from pediatric ALL patients. Our results provide unprecedented evidence that MLL-AF4 fusion transcripts can be present in normal hematopoietic cells, indicating that their expression is insufficient for leukemic transformation of normal lymphocyte precursors.