PubMed Health⌕ Search

Biomedical subjects

H D Preisler

Publications and source records attributed to H D Preisler.

At least 109 records · Page 6Linked to original sources
PubMed1989

Proto-oncogene expression during early myeloid differentiation of normal peripheral blood progenitor cells.

Peripheral blood mononuclear cells cultured in liquid medium with fetal calf serum undergo differentiation to myeloblasts (7 days) and then mature granulocytes (14-21 days). This culture system was used to study proto-oncogene expression during pre-myeloblast myeloid differentiation. c-myc mRNA was present in the peripheral blood mononuclear cells placed into culture, fell during the first 2-4 days of culture and then rose between days 2-4 and day 7 of culture, prior to and coincident with the appearance of myeloblasts. Histone H3 mRNA was absent or present at very low levels at initiation of cultures, and then rose throughout the first 7 days of culture. c-fms mRNA was absent at initiation of cultures, and appeared on days 2-5 of culture, prior to the appearance of myeloblasts. c-fos mRNA was not detected during differentiation of peripheral blood mononuclear cells to myeloblasts. Elucidation of patterns of proto-oncogene expression during normal myeloid differentiation is a prerequisite for interpretation of proto-oncogene expression in myeloid leukemia cells.

Blotting, Northern↗
PubMed1989

Detection of BrdU in the regenerating bone marrow cells of a patient with AML.

A patient with acute myeloid leukemia received bromodeoxyuridine (BrdU) prior to remission induction therapy. Prior to therapy only leukemic blast cells were found to be labeled. The marrow was aplastic by day 17 with the marrow cavity being devoid of BrdU labeled cells. In contrast rare BrdU containing cells were noted in the paratrabecular and endosteal regions. As the marrow recovered, many regenerating cells contained BrdU, implying that normal stem cells must have been in S-phase at the time of BrdU infusion, and repopulation of marrow may be accounted for by the activity of only a few clones in remission.

Bone Marrow↗
PubMed1989

Involvement of bands 9q21-q22 in five cases of acute nonlymphocytic leukemia.

Five patients with acute nonlymphocytic leukemia (ANLL) with chromosomal aberrations involving bands 9q21-q22 are described. The abnormalities were an interstitial deletion in two cases of ANLL FAB type M4 and M4 with eosinophilia, a terminal deletion in two cases of M4 and M5 type ANLL, and a translocation in an M2 ANLL. A review of reported cases of ANLL with abnormalities of chromosome 9 revealed a clustering of breaks at the region 9q21-q22, suggesting a possible role for these bands in leukemogenesis.

Adult↗
PubMed1989

The frequency of long-term remission in patients with acute myelogenous leukaemia treated with conventional maintenance chemotherapy: a study of 760 patients with a minimal follow-up time of 6 years.

Remission duration associated with the administration of conventional maintenance chemotherapy to patients with acute myelogenous leukaemia was evaluated. The records of 760 patients who entered remission between 1974 and 1979 were reviewed. The median duration of remission was 1.1 years with 16% of patients remaining in remission at 8 years. The relapse curve was biphasic with a high rate of relapse during the first 2 1/2 years of remission followed by a much lower relapse rate thereafter. Leukaemic relapses were noted through 8 years of remission. A plateau phase indicating freedom from the risk of leukaemic recurrence is not clearly apparent yet but may exist after the eighth year of remission.

Adult↗
PubMed1989

Point mutations in both transforming and non-transforming codons of the N-ras proto-oncogene of Ph+ leukemias.

The distribution and frequency of point mutations in the first and second coding exons of the N-ras proto-oncogene was examined in 6 cases of Philadelphia positive (Ph+) hemopoietic malignancies. To increase the detection sensitivity of the mutations and to estimate more accurately the frequency of abnormal alleles in the hemopoietic cell population, a polymerase chain reaction (PCR)/shotgun cloning/double stranded DNA sequencing method was used. Mutations activating the ras oncogenes involving codon 61 were observed in 5 out of 6 cases; in one of these cases (CML3), mutation at codon 61 involved a two base transition. Mutations involving codon 59 were also observed in one case (CML1). In longitudinal studies of 3 cases of chronic myelogenous leukemia samples obtained at the time of initial diagnosis and 5 to 7 years later, a multiplicity of mutations were detected at the time of initial diagnosis prior to any therapy. In one case (CML3), a mutation in codon 61 detected at diagnosis was still present 5 years later, in a second case (CML1) a mutation in codon 61 appeared during the course of the disease and persisted for at least one year, and in the third case (CML2) a mutation in codon 61 was present at diagnosis but absent 5 years later. In one instance (CML1) a mutation in codon 59 was present at the time of initial diagnosis but was not detectable in later samples. Several other point mutations leading to aminoacid changes were scattered predominately through the second exon but were not consistently detected in longitudinal studies on cells from the same patient. The data suggest that there is considerable genetic instability in the 2nd exon of N-ras in the myeloid leukemias but in every case a small subset of cells contains the mutations and these cells do not have a proliferative advantage.

Adult↗
PubMed1989

Protooncogene expression and the clinical characteristics of acute nonlymphocytic leukemia: A Leukemia Intergroup pilot study.

Northern blot analysis was used to assess the level of expression of five protooncogenes and histone H3 in the bone marrow cells of patients with acute nonlymphocytic leukemia (ANLL). The relationship between the level of gene expression and the clinical characteristics of the disease and response to therapy was studied. The levels of expression of c-myc and c-myb are weakly correlated and are unrelated to French-American-British (FAB) type of ANLL. The levels of expression of c-fms, c-fes, and c-fos are highly correlated with each other and are highest in leukemia with a monocytic component (c-fms v FAB = .71, c-fes v FAB = .75). High levels of c-myc expression are associated with a high probability of not responding to remission induction therapy (P = .004). The converse is true for c-fms expression levels. High levels of expression of c-myc or c-myb are associated with short remissions (P = .059 and .065, respectively), perhaps because they are associated with a high capacity for leukemic cell self-renewal and/or an inability of leukemic cells to differentiate in response to chemotherapy.

Bone Marrow↗
PubMed1988

Translocation (2;7)(p13;q36) in a case of acute nonlymphocytic leukemia evolving from a myelodysplastic syndrome.

A case of acute nonlymphocytic leukemia with a new translocation, t(2;7)(p13;q36), as the sole karyotypic abnormality is reported. The patient's leukemia evolved from a cytogenetically normal myelodysplastic syndrome of 4 years' duration. Following treatment the patient entered complete remission with loss of the cytogenetically abnormal clone. Subsequent bone marrow analyses showed recurrence of the myelodysplastic syndrome with a normal karyotype. Although both chromosomes 2 and 7 are known to be involved in nonrandom karyotypic changes in human cancer and leukemia, t(2;7)(p13;q36) has not been reported previously.

Aged↗
PubMed1988

Sustained viability of acute myelogenous leukemia cells in liquid suspension culture correlates with occurrence of differentiation.

To examine the relationship between viability of acute myelogenous leukemia (AML) blasts in liquid suspension culture and the occurrence of myeloid maturation in culture, total and differential cell counts and viability as determined by trypan blue dye exclusion were followed over 21 days of culture. A significant positive correlation was found between viability of cells on day 21 of culture and percentage of mature cells present. These data suggest that myeloid maturation may be a mechanism by which AML cells maintain viability in an adverse environment.

Cell Differentiation↗
PubMed1988

Assessment of c-myc expression in individual leukemic cells.

The expression of the proto-oncogene c-myc was studied at the protein level in cells obtained from patients with AML and CML. In florid AML and during the blastic phase of CML the majority of cells contain c-myc protein with the amount of protein differing widely among the cells of individual patients. In contrast, during complete remission in AML and during the chronic phase of CML cells containing c-myc protein are rare. Several studies demonstrated a discordance in the amount of c-myc transcript and the amount of c-myc protein present in cell populations thereby suggesting the presence of translational or post-translational regulation of c-myc expression. Further, the data suggest that high levels of c-myc protein in the leukemic cells of AML patients are associated with a poor response to therapy and that high levels in AML patients in CR or in the peripheral blood of chronic phase CML patients may be indicative of impending acute leukemia.

Gene Expression Regulation↗
PubMed1988

An acquired Robertsonian translocation dic(14;14)(p11;p11) in a patient with a myelodysplastic syndrome following treatment of multiple myeloma.

Acquired Robertsonian translocations are considered to be very rare chromosome changes in human malignancy, and only three cases have been described. We report a dic(14;14)(p11;p11) in a patient with myelodysplastic syndromes (MDS) following treatment for multiple myeloma. This patient also had other complex chromosomal abnormalities. The pattern of karyotype evolution in this patient was established by a series of cytogenetic studies. The relationship of the complex chromosomal changes to MDS following treatment for multiple myeloma is discussed.

Aged↗
PubMed1988

A hypothesis regarding the development of acute myeloid leukemia from preleukemic disorders. The role of protooncogenes.

Acute nonlymphocytic leukemia is often preceded by a preleukemic phase that can be characterized by a reduction in hematopoiesis, by ineffective hematopoiesis, or by a myeloproliferative/myelodysplastic state. The time between onset of the preleukemic state and the appearance of leukemia is quite variable, and at times such evolution does not occur. These clinical observations are compatible with the multistep hypothesis of tumor development. In studies underway in our laboratory, chronic myelogenous leukemia (CML) is being used as a model system to study the steps in and possible mechanisms underlying the development of preleukemia and its evolution to acute leukemia. Chronic myelogenous leukemia is particularly suited for this role because the chronic phase of the disease is an easily identifiable myeloproliferative state that invariably evolves into acute leukemia. In the discussion that follows, this clinical entity is used to develop a general model for the preleukemias and their evolution to acute leukemia.

Blast Crisis↗
PubMed1988

Enhanced expression of the granulocyte-macrophage colony stimulating factor gene in acute myelocytic leukemia cells following in vitro blast cell enrichment.

Expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene in acute myelocytic leukemia (AML) was assayed by Northern blot analysis. GM-CSF messenger RNA (mRNA) was detected in the freshly obtained mononuclear cells of only one of 48 cases of AML, in contrast with recent reports that GM-CSF mRNA might be detected in half of the cases of AML when RNA is prepared from T-cell- and monocyte-depleted leukemic cells. We did find, however, that expression of the GM-CSF gene was detectable in five of ten cases after in vitro T-cell and monocyte depletion steps. Additional studies suggest that expression of GM-CSF in the bone marrow of the one positive case, rather than being autonomous, was under exogenous control, possibly by a paracrine factor secreted by marrow stromal cells. These studies emphasize the potential for altering in vivo patterns of gene expression by in vitro cell manipulation.

Cell Separation↗
PubMed1987

Differing patterns of human protooncogene expression in peripheral blood and bone marrow acute leukemia cells.

The levels of protooncogene RNA in matched bone marrow and peripheral blood cells obtained from patients with newly diagnosed acute myelogenous leukemia were compared. While the absolute amounts of c-myc RNA in the matched specimens are similar, the levels are not correlated. In contrast, while the levels of c-fos RNA in the matched bone marrow and peripheral blood cells are correlated, the absolute levels of c-fos RNA differ substantially. The level of histone H3 RNA is higher in bone marrow cells than in peripheral blood cells. These substantial differences in protooncogene RNA levels between leukemic cells found in the bone marrow and in the peripheral blood make it impossible to accurately "characterize" gene expression in leukemic cells if studies are restricted to the cells in either compartment. Additionally, there appears to be a significant relationship between the levels of c-fos RNA and triose phosphate isomerase RNA and the height of the white blood cell count and between the level of c-fos RNA in marrow cells and the proportion of monocytic cells present.

Bone Marrow Cells↗
PubMed1987

Expression of the protooncogenes c-myc, c-fos, and c-fms in acute myelocytic leukemia at diagnosis and in remission.

RNA transcript levels of the protooncogenes c-myc, c-fos, and c-fms were measured in bone marrow cells obtained from patients with acute myelocytic leukemia at diagnosis or in complete remission. As controls, normal bone marrow cells were studied. The c-myc RNA levels are significantly higher in acute myelocytic leukemia cells at diagnosis than in remission or in normal marrow cells. In most instances the high c-myc RNA levels are a reflection of the high proportion of immature cells present in leukemic marrows. The bone marrow cells of several patients contain extremely high levels of c-myc RNA, levels which cannot be accounted for by the proportion of immature cells present in the bone marrow. The leukemic cells of patients with morphologically indistinguishable leukemias manifest different patterns of c-myc, c-fos, and c-fms expression. This observation is consistent with differences in behavior of leukemic cells even among patients with the same French-American-British type of leukemia. The normal-appearing bone marrow cells of some acute myelocytic leukemia patients in complete remission differ from normal bone marrow cells in having slightly higher c-myc RNA levels, as well as in the pattern of expression of c-fos and c-fms. The possible use of protooncogene expression patterns to subdivide the French-American-British categories of acute myelocytic leukemia into subtypes with greater prognostic significance is discussed.

Bone Marrow↗
PubMed1987

Analysis of cell cycle characteristics and course of the disease in ANLL.

The cell cycle characteristics of a newly diagnosed patient with acute nonlymphocytic leukemia (ANLL) were studied by using intravenous bromodeoxyuridine (BrdU) and our previously described "double-label" technique. The percentage of S-phase cells in the bone marrow (BM) biopsy were 25% compared to 7% from the simultaneously obtained BM aspirate. The duration of S-phase (Ts) was determined to be 4 hr and the total cell cycle time (Tc) was 16 hr. We demonstrated that the actual clinical course of this patient's illness corresponded well with the course predicted on the basis of these cell cycle measurements. Although he achieved aplasia in response to two successive courses of induction chemotherapy, leukemic cells repopulated the marrow, producing a rapidly rising PB white blood cell (WBC) count with a T1/2 of approximately 20 hr each time. It is likely that the resistance of this patient's leukemia to therapy was a result of the rapid proliferative rate of his leukemic cells and not due to the inability of chemotherapeutic agents to kill a large number of cells. Since the measurements can be completed within 48 hr, measuring Ts and Tc will provide a better understanding of the biological differences that exist between patients with ANLL.

Acute Disease↗
PubMed1987

Differentiation of myeloid cells in liquid culture: 2. Acute myelocytic leukemia cells.

In a companion paper we demonstrated that normal peripheral blood granulocytic precursor cells differentiate after 2-3 weeks in suspension culture. In the studies described here leukemic blast cells obtained from 14 patients with acute myelocytic leukemia (AML) and two patients with chronic myelocytic leukemia in blastic crisis were cultured in McCoy's 5A medium containing 15 per cent fetal bovine serum for 2-3 weeks at 37 degrees C in an atmosphere of 5 per cent CO2-95 per cent room air. 'Spontaneous' myeloid differentiation (20 x 10(4) viable mature myeloid cells ml-1) occurred in the cultures of cells obtained from 8 pts. The differentiation was granulocytic in three cases, monocytic in four cases and of mixed type in one case. Differentiation was independent of the growth of the cells in culture and occurred in four cases after the first week. Monocytic differentiation was seen only in AML of the FAB M4 type whereas granulocytic or mixed differentiation were seen only in AML of the FAB M1 or M2 types. When PHA leucocyte conditioned medium (PHA-LCM) was added to the cultures monocytic/macrophage differentiation was favoured. Inducers of the differentiation of the HL-60 cell line (N-methylacetamide, cytosine arabinoside, or retinoic acid) had no consistent effect on the differentiation and were at times inhibitory. Three patients received therapy with low dose cytosine arabinoside and no correlation was observed between the outcome of the treatment and leukemic cell differentiation in culture in the presence of the drug.

Bone Marrow↗
PubMed1987

Abrogation of the prognostic significance of low leukemic cell retention of cytosine arabinoside triphosphate by intensification of therapy and by alteration in the dose and schedule of administration of cytosine arabinoside.

The ability of leukemic cells to phosphorylate cytosine arabinoside (araC) and retain the triphosphate form of the drug (araCTP) is strongly predictive of remission duration for patients with acute nonlymphocytic leukemia who are treated with araC-based maintenance therapy. An increase in the intensity of therapy improves the overall median duration of remission, the increased intensity of therapy being especially beneficial for patients whose leukemic cells do not retain araCTP. This alteration in therapy reduces the prognostic significance of leukemic cell araCTP retention. Further, it seems that the use of high-dose araC as intensive consolidation therapy and the administration of conventional-dose araC by continuous infusion make it possible to further reduce or even abrogate the adverse prognostic significance of low leukemic cell retention of araCTP.

Acute Disease↗