20p12.3

DEE12,EIEE12,PI-PLC,PLC-154,PLC-I,PLC-beta-1,PLC154,PLCB1A,PLCB1B

Myelodysplastic Syndrome

Transition from Myelodysplastic Syndrome to Acute Myeloid Leukemia

In patients with normal GTG banding karyotype affected by Myelodysplastic Syndrome (MDS) (9 patients) and with Acute Myeloid Leukemia (AML) (6 patients), a monoallelic loss of the PLCB1 gene was detected. All the MDS patients, even though with normal karyotype, belonged to the high-risk group as scored by IPSS and FAB classifications. Out of 9 MDS patients with normal karyotype 4 had monoallelic deletion of the PLC beta1 gene, and all 4 died within 1 to 6 months after developing AML, compared to survival of over 30 months in the 5 MDS patients without the deletion. Two of 6 AML patients with normal karyotype had a monoallelic deletion of the PLCB1 gene; these 2 patients had a reduced survival (1 to 12 months) compared to the AML patients without the deletion (20 to 29 months). These evidences suggest a possible role for PLC beta1 in the progression of MDS to AML in high-risk patients.

Worse in patients having the deletion of the PLC beta1 gene.

FISH performed using a 115.000 bp probe (PAC clone 881E24) spanning from exon 19 to 32 of the gene.
FISH analysis, using KIAA 0581, i.e., part of human PLC beta1 cDNA, of human metaphases showing signals on both chromosomes 20 at band p12. (a) Q-Like banding; (b) fluorescence signals detected by FISH; (c) a partial karyotype along with a human chromosome 20 ideogram. (d) A schematic representation of the 1.9 cM interval, flanked by microsatellite markers D20S917 and D20S977, to which human PLC beta1 maps.

PLC beta1 is a key player in the control of cell cycle, namely the physiological progression through the G1 phase, in that the nuclear PLC beta1 evoked signalling targets the cyclin D3/cdk4 complex which phosphorylates retinoblastoma protein (pRb) that in turn activates the transcription factor E2F-1. Possibly alterations of this pathway could be involved in malignancies.