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Biomedical subjects

V Najfeld

Publications and source records attributed to V Najfeld.

At least 73 records · Page 4Linked to original sources
PubMed1984

Confirming evidence for the clonal development and stem cell origin of Philadelphia chromosome-negative chronic myelogenous leukemia.

A 74-year old woman with Ph1-negative chronic myelogenous leukemia (CML) and heterozygous for glucose-6-phosphate dehydrogenase (G6PD) was studied. Both A and B types of G6PD were found in skin. In contrast, white blood cells and platelets showed only a single G6PD type A. These results provide further evidence that Ph1-negative CML has a stem cell origin and develops clonally.

Aged↗
PubMed1984

Evidence for a stem cell common to hematopoiesis and its in vitro microenvironment: studies of patients with clonal hematopoietic neoplasia.

The origin and nature of cells forming the in vitro microenvironment in long-term cultures of human marrow were studied in five patients with clonal myeloproliferative disorders who were heterozygous for glucose-6-phosphatase dehydrogenase (G6PD). The results showed that cells in the adherent stromal layer forming the in vitro microenvironment were derived from the same clonal progenitors involved by the neoplasm in the four patients whose diseases originated in multipotent stem cells. In contrast, stromal cells were derived from normal progenitors in a patient with acute non-lymphocytic leukemia whose clone showed differentiative expression confined to cells in the granulocytic lineage. Mixing experiments demonstrated that the G6PD type displayed by the adherent marrow stromal cells was not obscured by contaminating non-adherent hematopoietic cells or marrow fibroblasts. The data suggest the existence of a pluripotent cell in normal hematopoiesis that gives rise to hematopoietic cells and to their micro-environment.

Adult↗
PubMed1984

TdT-positive acute leukemia with monocytoid characteristics: clinical, cytochemical, cytogenetic, and immunologic findings.

Thirteen patients with acute leukemias that were difficult to classify by the use of cytochemical staining and terminal deoxyribonucleotidyl transferase (TdT) activity are reported. The phenotype of the leukemic cells was characterized by the presence of mature or early monocyte lineage antigens and intense Ia antigen expression detected by monoclonal antibodies, terminal deoxytransferase activity, and cytochemical features, including both Sudan black B and periodic acid-Schiff activity. The mean age of this group of patients was 60 years. Five patients had leukemia occurring after chemotherapy or radiotherapy of a prior malignant disease, and two patients had a refractory anemia prior to development of acute leukemia. These patients had a low response rate to chemotherapy. This series of leukemia appears to form a distinct nosologic entity, representing a leukemic transformation among early cells of the monocyte lineage, resulting in a predominant neoplastic cell that is less mature than either the French-American-British M4 acute myelomonocytic leukemia or M5 acute monoblastic leukemia. The presence of terminal deoxytransferase activity was interpreted as indicating the primitive state of the cells in the differentiation sequence, rather than as implying any significance with respect to lineage.

Acute Disease↗
PubMed1983

Chronic myelogenous leukemia. Prolonged survival with spontaneous decline in the frequency of Ph1-positive cells and subsequent development of mixed Ph1-positive and Ph1-negative blast crisis.

A 23-year-old man developed Ph1-positive chronic myelogenous leukemia in 1966. After two short courses of busulfan not associated with severe myelosuppression, the frequency of Ph1-positive metaphases in his bone marrow was 40%. Over the next eight years, he remained hematologically stable without further therapy. During that time there was a progressive decline in the frequency of Ph1-positive metaphases in his bone marrow to 3% by 1976. His disease subsequently transformed to an acute lymphoblastic leukemia. Cytogenetic studies of the marrow at the onset of blast crisis and of cultured marrow blast cells suggested that the blasts were a mixture of Ph1-positive and Ph1-negative cells. This patient was thus unique in that he demonstrated spontaneous decline in the frequency of Ph1-positive cells in his bone marrow and he developed blast crisis with an apparent mixture of Ph1-positive and Ph1-negative blasts. These findings demonstrate that a Ph1-positive cell clone may lose its proliferative advantage over Ph1-negative cells and raise the possibility that Ph1-negative cells persisting in patients with Ph1-positive chronic myelogenous leukemia may be abnormal and, like the Ph1-positive cells, may be susceptible to acute leukemic transformation.

Adult↗
PubMed1983

"Masked" Ph1 chromosome in a complex three-way translocation.

A patient with myelofibrosis was found to have a 46,XX,del(1)(q24),del(11)(p11),-22,+mar karyotype in unstimulated peripheral blood (PB) and spleen cells. On detailed cytogenetic examination it was determined that this patient had an apparently "masked" Ph1 chromosome contained in a complex three-way translocation. Since phytohemagglutinin (PHA)-stimulated PB and spleen cells were essentially normal, the masked Ph1 chromosome was assumed to be an acquired cytogenetic abnormality. The portion missing from the masked Ph1 chromosome was apparently translocated onto del(1). Thus, the detailed karyotype was 46,XX,t(1;11;22)(q24;p11;q11 or q12),t(1;22)(q24;q11 or q12). This complex rearrangement was present primarily in cells belonging to the granulocyte-macrophage cell lineage, whereas E-rosetting cells, and presumably T lymphocytes, had normal karyotypes.

Aged↗
PubMed1981

Acquired trisomy 12 and absent Y chromosome in a patients with acute undifferentiated leukaemia.

A 60-year-old man developed pancytopenia and then acute leukaemia. The neoplastic cells in marrow were undifferentiated by electron microscopy and by immunological and cytochemical markers. The only other cells present in marrow were lymphocytes, plasma cells, macrophages and non-haematopoietic elements. Prior to chemotherapy, cytogenetic analysis of marrow cells showed two karyotypically distinct cell populations, one with 45,X,--Y and the other with a 46,X,--Y,+12 karyotype. All marrow cells stimulated by protein-A from staphylococcus aureus were 46,X,--Y,+12. Phytohaemagglutinin-stimulated cells were normal, 46,XY. These findings suggest strongly that most of the undifferentiated leukaemic cells were missing the Y chromosome. A subpopulation of these leukaemic cells also had trisomy 12. These observations and previously published findings suggest that trisomy 12 occurs non-randomly in haematological disorders, and in particular, may be associated with B-lymphoid malignancy.

Bone Marrow↗
PubMed1981

Monosomy 7 in a patient with pancytopenia and abnormal erythropoiesis.

In 1976, a patient with pancytopenia was found to have a population marrow cells with monosomy of chromosome 7 (45,XY,-7). Over the next 3 years he had continued abnormal hematopoiesis consisting of erythroid hyperplasia, ring sideroblasts, megaloblastic changes, and an increased proportion of myeloblasts. Sequential chromosome studies consistently showed the same abnormality without further karyotypic change. From the present study and comparable cases in the literature, there appears to be a distinct subgroup of patients with myeloproliferative disorders showing dyserythropoiesis with monosomy of deletion of chromosome 7 in the marrow cells.

Bone Marrow↗
PubMed1981

Evidence for a multistep pathogenesis of chronic myelogenous leukemia.

To study the relationship of the Philadelphia chromosome (Ph1) to the pathogenesis of chronic myelogenous leukemia, multiple B-lymphoid cell lines were established from a patient with Ph1-positive leukemia who was heterozygous for the X-chromosome-linked enzyme glucose-6-phosphate dehydrogenase. Both A and B types of enzyme were found in a 1:1 proportion in normal tissues, but 45 of 63 (71%) Ph1-negative B-lymphoid cells lines derived from this patient showed only the single glucose-6-phosphate dehydrogenase (type B) found in the Ph1-positive leukemic clone. Furthermore, 8 of 33 analyzable lines with B-type enzyme had chromosomal aberrations compared to 0 of 14 lines with A-type glucose-6-phosphate dehydrogenase. These results provide evidence for the suggestion that some cells of the abnormal clone do not express the Ph1 abnormality. Thus, acquisition of Ph1 may not be a sufficient cause for the disease. It is possible that at least two steps are involved in the pathogenesis of Ph1-positive chronic myelogenous leukemia, one causing abnormal proliferation of a clone of pluripotent hematopoietic stem cells and the other inducing Ph1 in descendants of these progenitors.

B-Lymphocytes↗
PubMed1980

Chromosome analyses of lymphoid cell lines derived from patients with chronic lymphocytic leukemia.

To study chromosome complements of chronic lymphocytic leukemia cells, six Epstein-Barr virus-transformed lymphoid lines were established from two patients with this disease who were heterozygous for the X-chromosome-linked enzyme glucose-6-phosphate dehydrogenase (G6PD). Immunoglobulin and G6PD were used as markers of the leukemic versus normal cell origin of the cell lines. The two lines, derived from putative normal cells, had no chromosomal changes. In contrast, chomosome abnormalities were found in each of the four cell lines of presumed leukemic cell origin. Although the chromosome aberrations are not as specific as the Philadelphia chromosome, there appears to be non-random involvement in chronic lymphocytic leukemia of some chromosomes, such as the No. 12.

Cell Line↗
PubMed1980

Establishment of a lymphoid cell line from leukemic cells of a patient with chronic lymphocytic leukemia.

Two lymphoid cell lines were established from a patient with chronic lymphocytic leukemia by infecting blood cells with Epstein-Barr virus (EBV). Studies of morphology, glucose-6-phosphate dehydrogenase, malic enzyme, immunoglobulin, and chromosomes of the two lines indicated that one of them originated from leukemic cells while the other arose from residual normal blood cells. The morphology and capacity for immunoglobulin secretion in the line that arose from leukemic cells were similar to those found in EVB-carrying lymphoblastoid cell lines grown from patients without neoplasia and differed from those seen in fresh chronic lymphocytic leukemia cells. These observations suggest that the introduction of EBV into the leukemic cells may have caused them to differentiate in a fashion similar to that noted in normal B cells after exposure to EBV.

Cell Line↗
PubMed1980

Involvement of the B-lymphoid system in chronic myelogenous leukaemia.

Studies with glucose-6-phosphate dehydrogenase (G6PD) isoenzymes have demonstrated that chronic myelogenous leukaemia (CML) is a clonal disorder of pluripotent haematopoietic stem cells which are capable of differentiation to myeloid cells, monocytes, erthrocytes and platelets. It has been observed recently in G6PD heterozygous patients with chronic phase CML that the non-E-rosetting lymphocytes were restricted to a single enzyme type, indicating that some lymphoid cells must also arise from the leukaemic clone. Surface or cytoplasmic immunoglobulin could be detected in up to 46% of the cells of these isolated non-T-lymphocyte populations, which suggested that cells from the CML clone were capable of differentiating into B lymphocytes. To investigate this further, we established Epstein-Barr virus (EBV)-transformed B-lymphoblastoid cell lines derived from patients with CML and studied chromosomes and G6PD to determine whether progenitor B lymphocytes for any of the cell lines had originated from the CML clone. We report here direct evidence that immunoglobulin-synthesizing B lymphocytes can arise from the CML stem cell clone.

B-Lymphocytes↗
PubMed1980

Glutamic pyruvate transaminase phenotypes in polycythaemia rubra vera.

Glutamate pyruvate transaminase (GPT) has been studied in the red cells of 46 patients with a confirmed diagnosis of polycythaemia rubra vera (PRV). The red cells of many of the patients showed low levels of enzyme activity. This activity could be restored by in vitro incubation with pyridoxal phosphate suggesting that the effect was due to low levels of B6 rather than to a primary abnormality of the GPT. Patients with the lowest levels of GPT activity were likely to have clonal chromosomal abnormalities in the bone marrow cells, particularly 20q-. Among 43 patients in whom the GPT phenotypes could be determined by an electrophoretic method there was a marked deficiency of heterozygotes. This disturbance in phenotypic expression may be related to the clonal nature of the disease in PRV, the clone showing lack of response to homeostatic controls and irregularities of gene expression.

Alanine Transaminase↗
PubMed1980

Restoration of nonclonal hematopoiesis in chronic myelogenous leukemia (CML) following a chemotherapy-induced loss of the Ph1 chromosome.

After intensive chemotherapy, marrow cells of some patients with Philadelphia chromosome (Ph1) positive chronic myelogenous leukemia (CML) become partially or completely Ph1-negative. However, without a second marker for the neoplastic clone, it could not be determined if these Ph1-negative cells arose from normal progenitors or were still members of an abnormal clone. In the present study, a patient with Ph1-positive CML, also heterozygous for glucose-6-phosphate dehydrogenase (G6PD), was studied before and after intensive chemotherapy. Prior to treatment only G6PD type B was detected in the patient's red cells, platelets, and granulocytes, and all unstimulated marrow metaphases had Ph1. After four cycles of chemotherapy, 76% of marrow cells were Ph1-negative, and approximately 80% of the granulocytes were nonclonal by G6PD analysis. Thus, the frequency of nonclonal cells by G6PD analysis correlated closely with that of the Ph1-negative cells. The data indicate that intensive chemotherapy can restore nonclonal and presumably non-neoplastic hematopoiesis in CML.

Adult↗
PubMed1979

Chronic myelocytic leukemia (CML): failure to detect residual normal committed stem cells in vitro.

Granulocytic colonies grown in culture from marrow and peripheral blood from five patients with Ph1-positive CML and heterozygous at the G-6-PD locus were analyzed for G-6-PD in order to identify CFU-C that do not arise from the CML clone. The patients had both B and A enzymes in normal tissues, but their CML clones typed as B. Whereas about 50% of colonies from normal subjects heterozygous as the G-6-PD locus show type-A G-6-PD and 50% type B, only two of the 1308 colonies from the CML patients had type-A G-6-PD. These data provide little evidence for persistence of normal committed stem cells in CML, a finding in contrast to that made previously in polycythemia vera, another clonal stem cell myeloproliferative disorder.

Adult↗
PubMed1978

Chronic lymphocytic leukaemia: Clonal origin in a committed B-lymphocyte progenitor.

The glucose-6-phosphate dehydrogenase (G.-6-P.D.) types of isolated blood-cell populations and normal skin were determined in two patients with chronic lymphocytic leukaemia (C.L.L.) who were heterozygous at the G.-6-P.D. locus. Normal tissues from each patient manifested both A and B G.-6-P.D. types, but the C.L.L. B-lymphocyte preparation from one patient showed only a single enzyme type, and from the other patient it showed 95% activity of one G.-6-P.D. type. These observations confirm the supposition based on immunoglobulin-marker data that at the time of study C.L.L. has a clonal origin. In contrast to the B lymphocytes, granulocytes, erythrocytes, platelets, and T lymphocytes displayed both enzyme types in proportions similar to those found in skin. These findings indicate that C.L.L. involves committed B-lymphocyte progenitors. Thus, the disease stands in contrast to chronic myelocytic leukaemia and other myeloproliferative syndromes, all of which involve multipotent haemopoietic stem cells.

Aged↗
PubMed1978

Myelofibrosis with complex chromosome abnormality in a patient with erythrocytosis due to hemoglobin Rainier and treated with 32P.

A patient with familial erythrocytosis associated with Hemoglobin Rainier, and previously treated with 32P, developed myelofibrosis with a hyperdiploid chromosome clone in the myeloid cells (51,XX,+1,2q-(q33),+6,+9,+11,-19,+20q+,+mar 1.) This transformation from a benign disorder of differentiated erythrocytes to a malignant disorder may have been secondary to radiophosphorus therapy.

Chromosome Aberrations↗