Chronic Myelocytic Leukemia: Ultrastructural Histopathology of Bone Marrow from Patients in the Chronic Phase

1984 ◽  
Vol 6 (4) ◽  
pp. 307-317 ◽  
Author(s):  
Fumio Kuto ◽  
Takashi Nagaoka ◽  
Yoshihiko Watanabe ◽  
Masatoshi Hayashi ◽  
Yumi Horasawa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Phase ◽  
Chronic Myelocytic Leukemia ◽  
Myelocytic Leukemia

scholarly journals Allelotype Analysis in the Evolution of Chronic Myelocytic Leukemia

Blood ◽  
1997 ◽  
Vol 90 (5) ◽  
pp. 2010-2014 ◽  
Author(s):  
Naoki Mori ◽  
Roberta Morosetti ◽  
Stephen Lee ◽  
Susanne Spira ◽  
Dina Ben-Yehuda ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Tumor Suppressor Genes ◽  
Mononuclear Cells ◽  
Blast Crisis ◽  
Chronic Phase ◽  
Allelic Loss ◽  
Chronic Myelocytic Leukemia ◽  
Myelocytic Leukemia ◽  
Acrocentric Chromosomes ◽  
Genetic Events

Abstract To elucidate the genetic events that may play important roles in the progression of chronic myelocytic leukemia (CML), we performed allelotype analysis in 30 patients with CML as the disease transformed to accelerated phase or blast crisis (21 myeloid and 9 lymphoid cases). DNAs were extracted from slides of bone marrow smears or from freshly isolated bone marrow mononuclear cells. The DNAs from the same individuals in both chronic phase and either blast crisis or accelerated phase were analyzed at 82 microsatellite markers, which mapped to each of the autosomal arms except the short arms of the acrocentric chromosomes. Loss of heterozygosity (LOH) on at least one locus was observed in 21 of the 30 cases (70%) as the disease progressed. Frequent allelic loss of ≥ 20% of the informative cases was observed on chromosome arms 1p (35%), 7p (21%), 19p (20%), and 20q (29%). Allelic losses were also analyzed according to phenotypes. LOH of ≥ 20% was detected on 1p (29%), 18p (20%), and 20q (27%) in myeloid blast crisis, and on 1p (50%), 4p (25%), 7p (43%), 9p (29%), 18q (25%), 19p (43%), and 20q (33%) in lymphoid blast crisis. Serial cytogenetic information was available for most of our cases with LOH on these arms, and only one case had loss of both chromosomes 9 and 20. Fractional allelic loss, calculated for each sample as the total number of chromosomal arms lost/total number of arms with information, showed a median value of 0.06 and a mean of 0.098 (range 0 to 0.60). These results suggest that tumor suppressor genes especially on 1p, 7p, 19p, and 20q probably have an important role in the progression to blast crisis of CML.

scholarly journals Molecular Follow-Up of Disease Progression and Interferon Therapy in Chronic Myelocytic Leukemia

Blood ◽  
1997 ◽  
Vol 90 (12) ◽  
pp. 4918-4923 ◽  
Author(s):  
Dina Ben-Yehuda ◽  
Svetlana Krichevsky ◽  
Eliezer A. Rachmilewitz ◽  
Ayelet Avraham ◽  
Giuseppe A. Palumbo ◽  
...  
Keyword(s):  
De Novo ◽  
Methylation Status ◽  
Pcr Amplification ◽  
Chronic Phase ◽  
Restriction Enzymes ◽  
Cytogenetic Response ◽  
Interferon Α ◽  
Chronic Myelocytic Leukemia ◽  
Myelocytic Leukemia

Abstract We previously reported that the abl promoter (Pa) undergoes de novo DNA methylation in the course of chronic myelocytic leukemia (CML). The clinical implications of this finding are the subject of the present study in which samples of CML patients, including a group treated with interferon α (IFNα) were surveyed. The methylation status of the abl promoter was monitored by polymerase chain reaction (PCR) amplification of the Pa region after digestion with several site-methylation sensitive restriction enzymes. Some 74% of the DNA samples from blood and marrow drawn in the chronic phase were nonmethylated, similar to control samples from non-CML patients. The remaining 26% were partially methylated in the abl Pa region. The latter samples were derived from patients who were indistinguishable from the others on the basis of clinical presentation. Methylated samples were mostly derived from patients known to have a disease of longer duration (26 months v 7.5 months, P = .01). Samples of 30 IFNα-treated patients were sequentially analyzed in the course of treatment. Fifteen patients with no evidence of Pa methylation before treatment remained methylation-free. The remainder, who displayed Pa methylation before treatment, reverted to the methylation-free status. The outcome is attributed to IFNα therapy, as the Pa methylation status was not reversed in any of the patients treated with hydroxyurea. Methylation of the abl promoter indicates a disease of long-standing, most likely associated with a higher probability of imminent blastic transformation. It appears to predict the outcome of IFNα therapy far better than the cytogenetic response.

scholarly journals Constitutive expression of GATA-1, EPOR, alpha-globin, and gamma-globin genes in myeloid clonogenic cells from juvenile chronic myelocytic leukemia

Blood ◽  
1995 ◽  
Vol 86 (1) ◽  
pp. 323-328 ◽  
Author(s):  
E Privitera ◽  
R Schiro ◽  
D Longoni ◽  
A Ronchi ◽  
A Rambaldi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Leukemic Cells ◽  
Globin Genes ◽  
Chronic Myelocytic Leukemia ◽  
Beta Globin ◽  
Globin Mrna ◽  
Gamma Globin ◽  
Myelocytic Leukemia ◽  
Alpha Globin

Juvenile chronic myelocytic leukemia (JCML) is a rare disorder of early childhood. Characteristic of JCML are the progressive appearance of high levels of fetal hemoglobin (HbF), reflecting a true reversion to a fetal type of erythropoiesis, and the presence of colony-forming cells able to grow in vitro spontaneously in the absence of growth factors. To better understand the relationship between the erythroid abnormalities and the leukemic process, we analyzed the expression pattern of specific genes related to erythroid differentiation--GATA-1, EPOR, alpha-globin, beta-globin, and gamma-globin genes--in JCML peripheral blood (PB) cells and in vitro-derived colonies. Northern blot analysis of PB cells from five JCML patients indicated levels of GATA-1 transcripts much higher than those usually found in other types of leukemic cells, and S1 nuclease protection assay detected significantly increased expression of gamma-globin mRNA. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of single granulocyte-macrophage colony-forming unit (CFU-GM) colonies, obtained in vitro in the absence of added growth factors from four JCML patients, detected GATA-1, EPOR, and globin (alpha and gamma) transcripts in most of the colonies tested, in contrast with control CFU-GM from normal bone marrow, which were positive only for GATA-1. Single JCML colonies were tested for the presence of two different transcripts; whereas alpha- and gamma-globin genes appeared mostly coexpressed, beta-globin mRNA was detected only in a minority of the gamma-globin-positive colonies, indicating that the leukemic pattern of hemoglobin synthesis is mainly fetal. In addition, the leukemic cells occurring during blast crisis of one of our patients displayed the typical features of a stem cell leukemia (CD34+, CD19-, CD2-, myeloperoxidase-). In this sorted CD34+ population, we detected the presence of a marker chromosome, der(12)t(3;12), previously identified in bone marrow cells at diagnosis and an expression pattern superimposable to that of the JCML colonies, consistently displaying a high gamma-globin:beta-globin mRNA ratio. The expression of erythroid markers within populations of leukemic cells, both in vivo and in vitro, supports the hypothesis that abnormal JCML erythroid cells may originate from the same mutated progenitor that sustains the growth of the leukemic cells.

scholarly journals The Granulocyte Response to Endotoxin in Patients with Hematologic Disorders

Blood ◽  
1964 ◽  
Vol 23 (5) ◽  
pp. 581-599 ◽  
Author(s):  
JOHN C. MARSH ◽  
SEYMOUR PERRY
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Bacterial Endotoxin ◽  
Chronic Myelocytic Leukemia ◽  
Hematologic Disorders ◽  
Recent Onset ◽  
Myelocytic Leukemia ◽  
Normal Individuals

Abstract Sixty patients with disorders involving the bone marrow were tested with a purified bacterial endotoxin given intravenously. Their leukocyte and granulocyte responses were evaluated based on criteria established in normal individuals and in patients with leukocytosis. Results in patients with chronic myelocytic leukemia, untreated or in relapse, suggest that adequate granulocyte mobilization may still occur if the disease has been of recent onset or if the count has recently started to rise in spite of therapy. Patients in remission demonstrated adequate granulocyte reserves. Most patients with chronic lymphocytic leukemia in this study responded well with an increase in the number of granulocytes. Patients with multiple myeloma as a group showed inadequate granulocyte mobilization. This study demonstrates that endotoxin testing is useful for the evaluation of bone marrow granulocyte reserves in patients with hematologic disorders.

scholarly journals Serial in vitro bone marrow fibroblast culture in human leukemia

Blood ◽  
1983 ◽  
Vol 61 (3) ◽  
pp. 589-592 ◽  
Author(s):  
T Nagao ◽  
K Yamauchi ◽  
M Komatsuda
Keyword(s):  
Bone Marrow ◽  
Acute Leukemia ◽  
Colony Formation ◽  
Calf Serum ◽  
Culture Method ◽  
Fibroblast Culture ◽  
Human Leukemia ◽  
Chronic Myelocytic Leukemia ◽  
Myelocytic Leukemia

Abstract Human fibroblast colony formation from bone marrow was performed in liquid culture. Fetal calf serum was used as a stimulator of the fibroblast colony formation. The colony formation took place not only in normal donors, but also in patients with acute leukemia and chronic myelocytic leukemia. At the diagnosis of the disease, significant colony suppression was observed in most cases of acute leukemia, while the number of colonies increased in half of the cases of chronic myelocytic leukemia. However, there was no correlation between the colony-forming efficiency and the initial number of peripheral platelets or bone marrow megakaryocytes that contained growth-promoting factor. The number of colonies increased after chemotherapy, recovered at the stage of complete remission, and then decreased to low levels at relapse in the patients with acute leukemia; it decreased after treatment with busulfan in the patients with chronic myelocytic leukemia. This fibroblast culture method is useful for counting fibroblast colony-forming cells in the bone marrow of human leukemia.

Influence of M-BCR breakpoint sites on the duration of chronic phase in 100 patients with chronic myelocytic leukemia

1993 ◽  
Vol 70 (1) ◽  
pp. 39-47 ◽  
Author(s):  
Kimio Tanaka ◽  
Tetsuo Hashimoto ◽  
Nobuo Oguma ◽  
Hiroo Dohy ◽  
Nanao Kamada
Keyword(s):  
Chronic Phase ◽  
Chronic Myelocytic Leukemia ◽  
Myelocytic Leukemia

scholarly journals The Philadelphia chromosome in human macrophages

Blood ◽  
1977 ◽  
Vol 49 (3) ◽  
pp. 367-370 ◽  
Author(s):  
DW Golde ◽  
C Burgaleta ◽  
RS Sparkes ◽  
MJ Cline
Keyword(s):  
Bone Marrow ◽  
Natural History ◽  
Cell Line ◽  
Bone Marrow Cells ◽  
Philadelphia Chromosome ◽  
Mononuclear Phagocyte ◽  
Chronic Myelocytic Leukemia ◽  
Human Macrophages ◽  
Myelocytic Leukemia ◽  
History Of

Three patients with chronic myelocytic leukemia in different phases of the natural history of the disease were studied. Their bone marrow cells were cultured under conditions favoring macrophage proliferation, and parallel cytogenetic and cytochemical studies were performed. All cell metaphases examined contained the Ph1 chromosome at a time when more than 80% of these metaphases were in identifiable macrophages. We conclude that the mononuclear phagocyte cell line contains the abnormal chromosome in Ph1-positive chronic myelocytic leukemia.

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