Acquired Robertsonian translocations in two leukemia patients.

Robertsonian translocations were observed in two leukemia patients. The first case was a patient with chronic lymphocytic leukemia, who was found to have a rare Robertsonian translocation der(14;15)(q10;q10). The second case, a patient with acute myeloid leukemia, had multiple Robertsonian translocations: der(15)t(13;15)(q11.1;p11.1), der(14;22)(q10;q10), and dic(21;22)(p11.1;p11.1). Acquired multiple Robertsonian translocations have not been reported previously in leukemia.

Repression of AIM-1 kinase mRNA as part of a program of genes regulated by Mpl ligand.

Megakaryocytes give rise to platelets that are essential for thrombosis and hemostasis. During development, megakaryocytes undergo an endomitotic cell cycle by which they skip late anaphase and cytokinesis to yield high ploidy cells. This process is regulated by the c-Mpl receptor ligand. In the current study we used differential display PCR as well as degenerate cloning of kinases to identify part of the program of genes regulated during Mpl ligand-induced differentiation. Several of the induced genes were identified as encoding metabolic proteins as carnitine palmitolytransferase, while other altered genes were identified as encoding kinases. Of these, AIM-1 kinase mRNA was severely downregulated by Mpl ligand at the onset of polyploidy in megakaryocytes. This effect was not related to message stability, but rather to a change in transcriptional rate. These data point to the potential importance of the transcriptional regulation of the AIM-1 gene for promoting megakaryocyte polyploidization.

Cytogenetics investigation in childhood chronic myeloid leukemia.

Cytogenetics investigations, mostly from peripheral blood, were carried out in 30 children with CML. Amongst a sample of 30 patients, 18 had chronic myeloid leukemia of adult variety (ACML), while the remaining 12 children had the juvenile type of chronic myeloid leukemia (JCML). Sixteen (88.9%) out of the 18 patients suffering from ACML tested positive for the classical Philadelphia chromosome translocation t(9; 22). Of the remaining two ACML patients, one tested positive for t(9; 13; 22) while no visible chromosomal changes were observed in the other patient. The activity of Nucleolar Organizer Region (NOR) was significantly reduced in 11 (61.1%) of the 18 patients suffering from ACML, when compared to that of 21 normal healthy controls. Ten out of the 12 patients suffering from JCML had normal karyotypes, while monosomy 8 and 21 q deletion were seen in the remaining two patients respectively. Amongst the 30 CML patients, chromosomal abnormalities were observed in 19 patients. Variant Philadelphia chromosome translocation (9; 13; 22) and monosomy B were observed in ACML and JCML, respectively. In two ACML patients, cytogenetic studies were helpful in diagnosis of the disease.

Discrepant cytogenetic and fluorescence in situ hybridization results in a 26-year-old male with early T-cell acute lymphocytic leukemia.

Analyzable G-banded metaphases were normal in bone marrow from a 26-year-old male having 80% blasts. Fluorescence in situ hybridization (FISH) using the centromeric probe, D7Z1, revealed 85% of interphase cells with one signal for chromosome 7. Chromosome painting revealed a chromosome 7 rearrangement in a few metaphases that were otherwise unanalyzable. A repeat bone marrow confirmed 3 of 20 metaphases, by G-banding, to have multiple rearrangements and aneuploidy, including a large derivative chromosome involving a complex rearrangement of chromosomes 5, 7, and 9; that is, der(5)t(5;9)(q31;q13)ins(5;7)(p15;q?31q?34), with loss of most of chromosome 7 (7 pter-->7q?31); one normal 7 was present. Immunophenotyping characterized the patient's condition as an early T-cell acute lymphocytic leukemia (ALL), with a population of cells suggesting biphenotypic leukemia. He attained a complete clinical remission with chemotherapy. Six months after the initial presentation he received an allogeneic bone marrow transplant. Three months later a CNS relapse was followed by a bone marrow relapse. At this time, eight months after transplant, repeat study of his bone marrow revealed the majority of metaphases had structural and numerical chromosome abnormalities similar to the small clone in the earlier study, including der(5)t(5;9)ins(5;7), but with two normal 7s. FISH showed two 7-centromere signals in interphase. The patient expired one month later.

Fluorescence in situ hybridization to assess aneuploidy for chromosomes 7 and 8 in hematologic disorders.

Stored, fixed cell suspensions of bone marrows from 70 patients karyotyped over a three-year period for myelodysplastic syndrome (MDS) or related hematologic conditions were retrospectively studied in two series using centromeric probes for chromosomes 7 and 8. Series I consisted of patient samples with numerical and/or structural abnormalities of chromosomes 7 or 8, matched with chromosomally normal samples from about the same time period. Series II consisted of consecutive MDS patient samples as well as patient samples in which one or more cells had numerical or structural abnormalities of 7 and 8. In both series, probes for chromosomes 7 and 8 were applied in each case and at least 100 nuclei were scored for each probe for the distribution of one, two, or three signals. Twenty-seven cases had clonal abnormalities by routine cytogenetics (RC): 12 with monosomy 7; one with monosomy 8; five with trisomy 8; nine with clonal abnormalities other than 7 or 8 aneuploidy. Eleven cytogenetically normal cases gave abnormal interphase FISH (IF) results; one was subsequently confirmed by metaphase FISH analysis to have a clonal structural abnormality of chromosome 7; one case with a trisomy 8 clone, in remission by RC, showed 35% of cells by IF with three signals for chromosome 8; one case had heteromorphic chromosomes by FISH. Of eight remaining cases, five (four with -7 and one with +8 by IF) were among 22 cases of cytogenetically normal MDS. Three remaining cases (two with +8 and one with both +7 and +8 by IF) had AML or MPD. The high rate of possible undetected monosomy 7, among MDS cases in particular, suggests all MDS cases should be screened by IF.

Juvenile chronic myelocytic leukemia--report of 10 cases.

Ten children (five boys and five girls) with juvenile chronic myelocytic leukemia were seen over a period of 12 years (1980-1991) at the All India Institute of Medical Sciences, New Delhi. With the exception of one who was aged 4.5 years, all children were below 4 years of age (mean age 20.4 months). The presenting features included fever, bleeding secondary to thrombocytopenia, marked hepatosplenomegaly, and skin rash. The striking hematological features were anemia, thrombocytopenia, peripheral blood monocytosis, and normoblastemia. There was no significant myeloid proliferation in the bone marrow aspirate (mean M:E = 5:1), while erythroid proliferation was prominent along with monocytosis (mean 11.2%). Fetal hemoglobin was raised in 8 of the 10 patients (mean 14.1%). Long-term survival was poor, with maximum survival being 18 months in one case. New modalities of management of this rare entity are discussed.