Fibroblast colony-forming cells with high sensitivity to serum mitogen(s) exist in bone marrow of patients with chronic myelocytic leukemia

2009 ◽  
Vol 44 (5) ◽  
pp. 291-295 ◽  
Author(s):  
Akiro Kimura ◽  
Osamu Katoh ◽  
Hideo Hyodo ◽  
Shizuyo Kusumi ◽  
Atsushi Kuramoto
Keyword(s):  
Bone Marrow ◽  
High Sensitivity ◽  
Chronic Myelocytic Leukemia ◽  
Myelocytic Leukemia

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.

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.

Effectiveness of Imatinib Therapy for a Patient with Sickle Cell Anemia and Chronic Myelocytic Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2559-2559 ◽  
Author(s):  
Julia L. Close ◽  
Richard Lottenberg
Keyword(s):  
Bone Marrow ◽  
Tyrosine Kinase ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Clinical Course ◽  
Globin Gene ◽  
Imatinib Therapy ◽  
Chronic Myelocytic Leukemia ◽  
Gamma Globin ◽  
Myelocytic Leukemia

Abstract Abstract 2559 Poster Board II-536 Background: To date, hydroxyurea (HU) is the only FDA-approved agent to treat sickle cell anemia (SCA). There is a need to identify alternative agents to prevent the complications of sickle cell disease. Clinical observations of patients receiving medications for other indications may provide insights into new opportunities. We present the clinical course of a patient with SCA and chronic myelocytic leukemia (CML) treated with imatinib. Case Report: A 24 year old woman with hemoglobin (Hb) SS had a variably elevated white blood cell (WBC) count for 3 years. WBC counts ranged from 11–39 × 103/cu mm; differential typically included 65–75% neutrophils, 15–20% lymphocytes, 1–13% metamyelocytes, and 1–3% myelocytes. Consistent with previous values, Hb ranged from 9–11 g/dL, and platelet counts from 250–400 × 103/cu mm. Real-time PCR for BCR-ABL obtained from the peripheral blood was positive. Bone marrow biopsy showed a markedly hypercellular marrow with granulocytic hyperplasia. Blasts were not increased in number. Cytogenetic studies revealed 46 XX, t(9;22)(q34;q11.2) in 20/20 analyzed cells. Further characterization by fluorescence in situ hybridization (FISH) technique demonstrated the loss of chromosome 9 long arm material. BCR-ABL interphase FISH confirmed the presence of 9/22 chromosomal translocation, found in 279/300 interphase nuclei. The patient was diagnosed with SCA in early childhood. Molecular analysis of genomic DNA revealed homozygosity for Hb S and single alpha-globin gene deletion of the rightward type. There was no evidence for typical deletions associated with HPFH or delta-beta zero thalassemia. The C>T polymorphism at nt −158 in the G-gamma-globin gene promoter region and other known HPFH point mutations in the G- or A-gamma globin genes were not identified. Her clinical course has not been complicated by stroke, pulmonary hypertension or acute chest syndrome. Radiographic studies revealed evidence of multiple bony infarcts. She was hospitalized with painful episodes 1-2 times per year, until the age of 16. At that time, her frequency of hospitalizations for painful episodes increased to 3-5 times per year, and showed a temporal relationship to her menses. She was started on oral contraceptives and hydroxyurea (HU) at the age of 18. Subsequently, hospitalizations for painful episodes decreased to 0-2 per year. At the age of 22, hydroxyurea was held during pregnancy. After delivery, HU was reinitiated and continued until the diagnosis of CML. She was hospitalized for painful episodes two times in the 12 months preceding the diagnosis of CML. Imatinib mesylate monotherapy at 400 mg/day was initiated. Two weeks later, a hematologic response was documented. At one year, bone marrow cytogenetic and molecular complete responses were documented. In the 17 months since initiation of imatinib, the patient has had a significant reduction in the frequency of painful episodes. No hospitalizations have been required and the patient has had a reduction in daily pain allowing discontinuation of a transcutaneous electrical nerve stimulation unit. During imatinib therapy Hb levels ranged from 8.0 to 9.2 g/dL, WBC counts from 3.3–6.1 × 103/cu mm, and platelet counts from 114–205 × 103/cu mm. Hemoglobin electrophoresis results are shown in the table. Clinical Implications: To our knowledge, the clinical course of patients with SCA treated with imatinib has not previously been reported. Imatinib targets the BCR-ABL fusion tyrosine kinase, c-kit, and platelet-derived growth factor receptor. Myelosuppression is frequently noted as a side effect of this therapy. The improvement in this patient's sickle cell symptoms may be attributable to a reduction in the neutrophil count, as observed with HU therapy, but it is possible imatinib therapy had a positive effect on release of cytokines or other factors involved in vaso-occlusion. The Hb F level was not significantly increased with imatinib therapy. Evaluation of small molecule tyrosine kinase inhibitors in experimental models of SCA should be considered. Disclosures: No relevant conflicts of interest to declare.

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 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

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.

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