Inhibition of granulocyte-macrophage colony-stimulating factor prevents dissemination and induces remission of juvenile myelomonocytic leukemia in engrafted immunodeficient mice.

Granulocyte-macrophage colony-stimulating factor (GM-CSF ) and tumor necrosis factor alpha (TNFalpha) have been implicated in the pathogenesis of the fatal childhood disease termed juvenile myelomonocytic leukemia (JMML). We used a severe combined immunodeficient/nonobese diabetic (SCID/NOD) mouse model of JMML and examined the effect of inhibiting these cytokines in vivo with the human GM-CSF antagonist and apoptotic agent E21R and the anti-TNFalpha monoclonal antibody (MoAb) cA2 on JMML cell growth and dissemination in vivo. We show here that JMML cells repopulated to high levels in the absence of exogeneous growth factors.

Detection of minimal residual disease in an AML patient with trisomy 8 using interphase fish.

Patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) often exhibit clonal chromosomal abnormalities. Using a probe for the centromeric region of chromosome 8, fluorescence in situ hybridization (FISH) on interphase cells was used to detect trisomy 8 in an AML patient whose leukemia was characterised by the karyotype 47, XY, +8, del(9) (q21.1q32).

Apoptosis regulatory gene NEDD2 maps to human chromosome segment 7q34-35, a region frequently affected in haematological neoplasms.

Developmentally regulated mouse gene Nedd2 encodes a protein similar to the product of the nematode Caenorhabditis elegans cell death gene ced-3 and the mammalian interleukin-1 beta-converting enzyme. Overexpression of Nedd2 in cultured mammalian cells induces apoptosis that can be blocked by proto-oncogene BCL2. We have isolated cDNA clones for the human homologue of the mouse gene and, by using these as probes, mapped the human NEDD2 gene to 7q34-35 by fluorescence in situ hybridisation.

Paracentric inversion of chromosome 14 plus rare 9p variant in a couple with habitual spontaneous abortion.

A couple presenting with habitual spontaneous abortion both showed a chromosome rearrangement. The male had an apparently balanced paracentric inversion of chromosome 14 - 46,XY,inv(14) (q11q32). The female had a karyotype with a rare large short arm variant of chromosome 9 - 46,XX,var(9) (p11p21).