Monitoring of engraftment and progression of acute lymphoblastic leukemia in individual NOD/SCID mice.

OBJECTIVE: The aim of this study was to develop an animal model for human acute lymphoblastic leukemia (ALL) in which the kinetics and characteristics of leukemia can be sequentially monitored in individual mice. MATERIALS AND METHODS: NOD/SCID mice were inoculated intravenously with primary ALL. Progression of leukemia was monitored throughout the development of disease by determination of absolute leukemic cell counts (LCC) in peripheral blood. RESULTS: LCC as low as 10(4) leukemic cells/mL blood could be detected. ALL cells from 5 of 5 patients engrafted, and after identification of the first leukemic cells in peripheral blood, LCC increased exponentially. Leukemic cells showed specificity of homing to spleen and bone marrow, and LCC strongly correlated with the level of leukemic engraftment in these organs throughout disease progression, demonstrating that LCC are representative for overall leukemic burden. Cytogenetic analysis of leukemic cells recovered after six successive in vivo transfers revealed no major karyotypic changes as compared to primary cells, and selection of the dominant clones was observed. This selection process was reflected by an increase in the rate of leukemic progression as compared to the first inoculation, demonstrating the accuracy with which kinetics of leukemic progression can be studied by determination of LCC. CONCLUSIONS: This model is suitable for detailed studies of kinetics and characteristics of ALL in vivo, and it may be useful for monitoring effects of novel therapeutic regimens.

Chromosome 9 alterations and trisomy 22 in central chondrosarcoma: a cytogenetic and DNA flow cytometric analysis of chondrosarcoma subtypes.

Chondrosarcomas are malignant cartilaginous tumors. Most are located in the medullar cavity (central chondrosarcoma), and a minority develop in a preexisting osteochondroma (peripheral chondrosarcoma). The authors present karyotypes for 37 central, peripheral, juxtacortical, and dedifferentiated chondrosarcomas. Using loss of heterozygosity (LOH) analysis and DNA flow cytometry, the authors previously showed that central and peripheral chondrosarcomas probably evolve by different genetic mechanisms. Peripheral chondrosarcoma is characterized by genetic instability, as was previously shown by a high percentage of LOH and a broad range in DNA ploidy. The authors now show that all peripheral chondrosarcomas tested are aneuploid, combined with many nonspecific chromosomal aberrations. Two juxtacortical chondrosarcomas showed normal chromosome numbers combined with limited structural alterations, substantiating that juxtacortical and peripheral chondrosarcomas are two clinicopathologically different entities with a different genetic background. Central chondrosarcomas were previously found to be peridiploid with limited LOH, most frequent at 9p21. In the current study, chromosome 9 was involved in five of seven central chondrosarcomas compared with only one of four peripheral chondrosarcomas. Three central tumors showed involvement of the 9pl2-22 region, suggesting an important role for chromosome 9 in the oncogenesis of central chondrosarcoma. Moreover, trisomy 22 was found in four central chondrosarcomas only.

Ring chromosome 4 as the sole cytogenetic anomaly in a chondroblastoma: a case report and review of the literature.

Chromosome analysis of a chondroblastoma of the right distal femur in a 31-year-old male patient revealed a ring chromosome 4 in approximately one-third of the analyzed cells. The remaining cells had a normal karyotype. These findings were subsequently confirmed by fluorescence in situ hybridization (FISH) with a chromosome-4-specific library. FISH with cosmids pC847.351 (4p16.3) and cT171 (4q35) revealed that fewer than 300 kilobase pairs (kbp) are deleted. To our knowledge, ring chromosome 4 has never been reported in this type of neoplasm. There are, however, several reports of chondroblastoma with other chromosome abnormalities, but the relation of these anomalies to this tumor specifically is unclear. In this report, we also provide a review of the literature concerning cytogenetic studies in chondroblastoma. The possible significance of ring chromosome 4 in this type of tumor is discussed.

Prenatal and postnatal investigation of a case with Miller-Dieker syndrome due to a familial cryptic translocation t(17;20) (p13.3;q13.3) detected by fluorescence in situ hybridization.

We present here a case report of a fetus with a kidney anomaly and dilated occipital horns, detected initially by echoscopy at 29 weeks' amenorrhoea. After 31 weeks of gestation, the proband was born with clinical symptoms of Miller-Dieker syndrome. This was subsequently confirmed by fluorescence in situ hybridization (FISH), but not by conventional cytogenetic analysis. FISH using a cocktail of cosmids (c197-2, c197-4, c197-9) from the Miller-Dieker critical region showed a deletion of 17p13.3 in one homologue of chromosome 17. Additional FISH studies revealed a subtle 17p;20q translocation in the father, his sister, and the paternal grandmother. Hence, our patient is a carrier of an unbalanced 17;20 translocation resulting in a partial deletion of 17p and a partial trisomy 20q. Whenever kidney anomalies and dilated occipital horns are observed together with polyhydramnios during prenatal ultrasound examination, the possibility of Miller-Dieker syndrome should be suspected. In such cases, prenatal and/or postnatal chromosome studies should also include FISH analysis with the appropriate probes.

18q- and 18q+ mosaicism in a mentally retarded boy.

A mentally retarded boy was found to have an unusual chromosomal mosaicism [46,XY, del(18) (q22)/46,XY,iso psu dic(18)(q23)]. The clinical manifestations are compatible with the 18q- syndrome. The chromosome alteration was defined by high resolution banding and fluorescence in situ hybridization (FISH). A mechanism to explain the origin of the two cell lines is presented and discussed.