Partial trisomy 17q22-qter and partial monosomy Xq27-qter in a girl with a de novo unbalanced translocation due to a postzygotic error: case report and review of the literature on partial trisomy 17qter.

Partial trisomy 17q22-qter is a rare but well-recognized clinical entity. We present a case of partial trisomy for the long arm of chromosome 17, which was detected in a female infant with severe psychomotor and somatic retardation, Stargardt disease, short limbs, and numerous minor anomalies. Differential chromosomal staining demonstrated an excess of genetic material on the long arm of the late replicating X chromosome. FISH and DNA polymorphism analysis showed that the extra material belonged to the distal part of the long arm of chromosome 17 and that there was a partial monosomy of the distal part of the long arm of the derivative X chromosome. The breakpoint regions of this translocation were identified by molecular analysis using polymorphic microsatellite markers on human chromosomes 17 and X. The origin of the abnormal X chromosome was found to be paternal, whereas the origin of the duplicated part of chromosome 17 was maternal. The unbalanced translocation between the paternal X and the maternal chromosome 17 is, therefore, suggested to be due to a postzygotic error.

Early human trophoblast cell cultures. A morphological and immunocytochemical study.

Rapidly growing cytotrophoblasts were isolated from early human chorionic villi and the Papanicolaou method was used to characterize their cytology and transformation into syncytiotrophoblasts. Cytotrophoblasts fused and formed binucleated cells or mononucleated intermediate cells. Syncytial cells were formed by fusion of small cytotrophoblasts or intermediate cells and cytotrophoblasts. Glycosaminoglycans were produced in cytotrophoblasts and released extracellularly. Here they were accumulated and/or diffused into a continuous layer covering the cells. Glycosaminoglycans in syncytial cells were contained in well defined membranous sacs. Cytotrophoblasts only grown beyond confluence differentiated into villi with a villus-like histology.

Acute promyelocytic leukemia relapsing into FAB-M2 acute myeloid leukemia with trisomy 8.

Acute promyelocytic leukemia was diagnosed in a 48-year-old man; the karyotype was normal, whereas reverse transcriptase polymerase chain reaction (RT-PCR) analysis identified PML/RAR alpha chimeric transcripts of the bcr3 type. Rather unexpectedly, the patient did not respond to alltrans retinoic acid administration; he attained complete remission with conventional chemotherapy and became PML/RAR alpha negative. Two years later, while PML/RAR alpha negative on RT-PCR, he presented with thrombocytopenia. Bone marrow examination was compatible with myelodysplasia of the RAEB type; the karyotype was normal. Then, after 10 months, he developed overt acute myeloid leukemia with PML/RAR alpha negative, French-American-British M2 blasts; karyotypic analysis revealed mosaicism for trisomy 8.

An unusual cytogenetic abnormality involving chromosomes 1 and 7 in a case of chronic myelomonocytic leukemia.

We report a case of chronic myelomonocytic leukemia in which cytogenetic analysis revealed a 47,XY, +1, +der(7)del(7)(q32q36)ins(7;1)(q32;p36.3p22) chromosomal constitution. This abnormal karyotype, which as a whole is new to any myeloid malignancy, points to a possible pathogenetic role for the oncogenes MET and FGR on the derivative chromosome 7, and for the CSF1 and JUN genes flanking the breakpoint on chromosome 1.

A novel chromosomal abnormality involving chromosomes 2 and 18 in a patient with myelodysplastic syndrome.

Cytogenetic analysis of bone marrow cells from a patient with myelodysplastic syndrome associated with eosinophilia showed a complex translocation with a 46,XY,t(2;18;2)(p23;q11;q32) karyotype. The patient has refractory anemia (RA) according to the French-American-British Cooperative Group (FAB) classification, and after 90 months of follow-up he shows no evidence of leukemic transformation. This chromosomal abnormality has not been previously described in myelodysplastic syndromes and may be associated with good prognosis as the patient has been stable for a long time.

Hypereosinophilia associated with monosomy 7.

Cytogenetic analysis of bone marrow cells from a patient with anemia, marked leukocytosis with eosinophilia, and thrombocytopenia showed monosomy 7 in all metaphases examined. The patient has refractory anemia (RA) according to FAB classification. Because of the hypereosinophilia of the patient, PCR technique was performed and no bcr-abl mRNA, specific for chronic myelogenous leukemia, was detected. Monosomy 7 has not been previously described in cases with hypereosinophilia. We assume, according to previous reports, that multiple genetic lesions can be involved in the pathogenesis of hypereosinophilia in this patient.

Trisomy 11 with loss of the Y chromosome and trisomy 13 in a case of de novo acute myeloid leukemia.

We report a man with de novo acute myeloid leukemia (M4 of the FAB classification) bearing two abnormal clones in the bone marrow cells. The clones showed trisomy 11 with loss of the Y chromosome and trisomy 13, respectively.

Molecular demonstration of BCR/ABL fusion in two cases with chronic myeloproliferative disorder carrying variant Philadelphia t(14;22)(q32;q11).

We report two cases with chronic myeloproliferative disorder which were found to carry simple variant Philadelphia (Ph) t(14;22)(q32;q11) in unstimulated bone marrow mononuclear cells. Both cases were characterized molecularly by Southern blot, reverse transcription-polymerase chain reaction (RT-PCR), and direct sequencing of the RT-PCR products. In the first case (female, aged 65, in blastic transformation which developed one year after the initial diagnosis of myelofibrosis), a t(14;22) (q32;q11) was found in association with several other chromosomal abnormalities [48,XX,+X,+5,del(5) (q12q32),+8,der(9)t(9;11)(q32;q11),-11]; molecular analysis demonstrated the presence of a BCR-ABL chimeric gene and mRNA transcript of the b2-a2 type. In the second case (female, aged 16, with clinical and hematologic features typical of chronic myelogenous leukemia in chronic phase), a t(14;22) (q32;q11) was identified as the sole karyotypic abnormality; again, molecular analysis demonstrated the presence of a BCR-ABL chimeric gene and mRNA transcript, this time of the b3-a2 type. Our findings further support the notion that, even when undetectable by conventional cytogenetics, band 9q34 participates in all Ph chromosomes and leads to the formation of chimeric BCR-ABL genes.

Cytogenetic analysis and RAS mutations in primary myelodysplastic syndromes.

Cytogenetic analysis was performed in 60 patients with primary myelodysplastic syndromes--diagnosed, treated, and followed in our department. In 41 cases, the presence of the NRAS mutation was also evaluated. The aim of this study was to evaluate the prognostic value of chromosomal abnormalities and NRAS mutation. The median age of the patients was 67 years (18-88 years), and the French-American-British classification was as follows: refractory anemia 26, refractory anemia with ring sideroblasts 4, refractory anemia with excess of blast cells 15, refractory anemia with excess of blast cells in transformation 3, and chronic myelomonocytic leukemia 12. Survival analysis was performed for the patients with a normal (n = 35), an abnormal (n = 25) karyotype and with a single (n = 15) or multiple (n = 10) cytogenetic abnormalities. Abnormal karyotypes were detected in 25 of the 60 patients (41.6%). Fifteen of these patients had a single and 10 had two or more lesions. The median survival of the patients with a normal (33.1 months) and with an abnormal (36.5 months) karyotype was not significantly different. Patients with multiple lesions had a reduced median survival compared with patients with single anomalies (19.2 versus 39.7 months, p = 0.5). Patients with an abnormal karyotype progressed to acute leukemia more frequently compared with patients without lesions (36 versus 28.6%, p = 0.5). NRAS mutation was detected in 2 of 10 CMMoL patients studied and in none of the 31 patients with other types of myelodysplastic syndrome. Marrow blasts more than 10% significantly affected survival.

[Molecular analysis of the parental origin of trisomy in two families with two children having regular trisomy 21]. / Analyse moléculaire de l'origine parentale de la trisomie dans deux fratries comportant deux enfants atteints de trisomie 21 libre.

In order to investigate the parental origin of the trisomy in two families with two free trisomy 21 affected siblings, cytogenetic and molecular analyses were performed. In each case the parental origin was the same for both patients. In one of the families an association between the concordance of the paternal origin of the trisomy and the existence of mosaicism in the blood was established. The various etiologies which may account for recurrence are discussed.