Changes in Oncogene Expression Implicated in Evolution of Chronic Granulocytic Leukemia from its Chronic Phase to Acceleration

1998 ◽  
Vol 30 (3-4) ◽  
pp. 293-306 ◽  
Author(s):  
ZoltÁN Beck ◽  
Attila Bácsi ◽  
Eszter Kovács ◽  
JolÁN Kiss ◽  
Attila Kiss ◽  
...  
Blood ◽  
1976 ◽  
Vol 47 (6) ◽  
pp. 1003-1009 ◽  
Author(s):  
GP Canellos ◽  
VT DeVita ◽  
J Whang-Peng ◽  
BA Chabner ◽  
PS Schein ◽  
...  

Abstract Thirty-two patients in the blastic phase of Philadelphia chromosome- positive chronic granulocytic leukemia (CGL) were studied in a prospective randomized trial in which vincristine--prednisone (19 patients) was compared with cytosine arabinoside--6-thioguanine (13 patients). Seven remissions (37%), including two complete remissions, were achieved in the vincristine--prednisone group. Three of the five with predominant hypodiploid blast cell lines treated with vincristine-- prednisone had complete or partial remissions. Both complete remitters presented with hypodiploidy consisting of 44 chromosomes. Four patients (30%) who were treated with cytosine arabinoside--6-thioguanine responded with one complete remission. The median survival of the responders was 8 mo, as compared to 1--2 mo for the nonresponders. Crossover to the opposite regimen as secondary therapy following refractoriness or resistance resulted in only 3 partial responses out of 21 treated. All three had previously responded to vincristine-- prednisone. Of the 32 cases, 14 had an elective splenectomy during the chronic phase of the disease. Prior splenectomy did not influence the response to chemotherapy, as all three complete remitters occurred in the nonsplenectomized group. Similarly, survival in the blastic phase was not affected by prior splenectomy.


1986 ◽  
Vol 72 (3) ◽  
pp. 313-316
Author(s):  
Indira Sahdev ◽  
Ram S. Verma ◽  
Harvey Dosik

A case of Philadelphia (Ph')-chromosome-positive acute leukemia (AL) is presented who went into remission with disappearance of the Ph1 chromosome and later on developed the chronic phase of chronic granulocytic leukemia (CGL) with reappearance of the Ph1 chromosome. The patient is alive 6+ years following the diagnosis. The entity of Ph1-positive AL is discussed. It is suggested that the patients with Ph1-positive AL who develop CGL have a better prognosis than previously described.


Blood ◽  
1975 ◽  
Vol 45 (2) ◽  
pp. 197-203
Author(s):  
GP Canellos ◽  
RC Young ◽  
PE Neiman ◽  
VT Jr DeVita

Dibromomannitol (DBM) is a new agent for the treatment of chronic granulocytic leukemia. A propsective evaluation of the drug was undertaken in a randomized comparison with busulfan. Forty previously untreated, Philadelphia chromosome-positive cases were treated, with 20 patients in each treatment group. The protocol provided for continuous maintenance therapy after remission induction, with a crossover to the opposite drug in patients who became refractory to the primary agent but are without evidence of blastic tranformation. There were 14 remissions in the DBM group and 15 in those treated with busulfan. The rate of decrease of the elevated leukocyte count was more rapid with DBM, but prolonged disease control off treatment occurred in only three of 14 cases as opposed to nine of fifteen busulfan-treated patients who required a median delay of 12 mo before maintenance could be initiated. Hypoplasia occurred in one DBM patient and two busulfan cases. Following recovery, crossover to the opposite drug in two cases again resulted in hypopllasia. Increased skin pigmentation, amenorrhea, pulmonary fibrosis, and cytologic dysplasia, commonly associated with busulfan adminstration, were also noted with DBM. The median duration of disease control with busulfan was 34 mo and 26 mo with DBM. There was no signigicant difference in the incidence of blastic transformation, and median survival for both groups was 44 mo. DBM appears to be as effective as busulfan in the treatment of the chronic phase of CGL but with a more predictable myelosuppressive action. The principal advantage of busulfan over DBM is the fact that more than half the busulfan-treated patients experienced prolonged disease control off treatment.


Blood ◽  
1982 ◽  
Vol 60 (6) ◽  
pp. 1447-1452 ◽  
Author(s):  
F Frassoni ◽  
A Bacigalupo ◽  
M Podesta ◽  
MT Van Lint ◽  
G Piaggio ◽  
...  

Abstract T lymphocytes were derived by E rosetting from the peripheral blood (PB) and bone marrow (BM) of 15 patients with chronic granulocytic leukemia (CGL) in the chronic phase of their disease. T cells were also obtained from 12 healthy individuals. T cells were incubated overnight either in culture medium (RPMI) or RPMI plus pokeweed mitogen (PWM). The supernatants were then recovered and the cells washed in fresh RPMI. T cells from normal donors and from CGL patients were then cocultured with normal allogeneic marrow cells grown in soft agar for CFU-C colony formation. Target marrow cells were also grown in agar in the presence of T-derived supernatants. The results of this study can be summarized as follows. (1) Normal PB and BM T cells efficiently suppressed autologous and allogeneic CFU-C growth after PWM stimulation. (2) T cells derived from peripheral blood or marrow of CGL patients failed to inhibit CFU-C growth, whether pretreated with PWM or not. (3) The supernatants of PWM-treated normal T cells strongly inhibited CFU-C colony formation, whereas the supernatants of PWM- treated CGL T cells had no CFU-C/suppressor activity. These data indicate that T cells from CGL patients cannot be primed to become CFU- C suppressor cells after PWM: stimulation in vitro and cannot release a soluble inhibitor of granulopoiesis produced by PWM-primed normal T cells.


Blood ◽  
1953 ◽  
Vol 8 (4) ◽  
pp. 375-381 ◽  
Author(s):  
HAROLD SHUB ◽  
MAURICE M. BLACK ◽  
FRANCIS D. SPEER

Abstract 1. An additional case of coexistent pregnancy and chronic granulocytic (myelogenious) leukemia is reported. 2. Coincident with pregnancy the leukemia in this patient underwent a transition from the chronic phase in remission to acute myeloblastic disease with rapid exitus. 3. The pertinent literature concerning pregnancy and chronic granulocytic leukemia has been reviewed and evaluated. 4. Our findings indicate that pregnancy may have a deleterious effect on the course of the patient with chronic granulocytic leukemia, and may initiate an acute exacerbation of the disease. 5. In approximately one-third of the cases of chronic granulocytic leukemia complicated by pregnancy, an exacerbation and death occurred within eight months postpartum. 6. In chronic granulocytic leukemia, pregnancy should be avoided.


2019 ◽  
pp. 633-638
Author(s):  
K. Smetana ◽  
H. Klamová ◽  
D. Mikulenková

The present study was undertaken to estimate the approximate size of nuclear regions occupied by nucleolar bodies during the cell differentiation and maturation. The differentiation and maturation of human leukemic granulocytic cells in patients suffering from the chronic phase of the chronic granulocytic leukemia (CML) represented a convenient model for such study because of the large number of cells for the diameter measurements at the single cell level. Early and advanced differentiation or maturation stages of these cells are well defined and nucleolar bodies and nuclear outlines are easily seen by simple cytochemical methods for the visualization of RNA and silver stained proteins in smear preparations. During the cell differentiation and maturation, the estimated size of the nuclear region occupied by nucleolar bodies decreased in both untreated and treated patients with the anti-leukemic therapy. However, the size reduction of nucleolar bodies in differentiated and mature cells was larger than that of the nucleus. In addition, the results also indicated that the nuclear region occupied by nucleolar bodies was characteristic for each differentiation and maturation stage of the granulocytic cell lineage and was not substantially influenced by the anti-leukemic therapy of CML patients.


Blood ◽  
1975 ◽  
Vol 46 (1) ◽  
pp. 11-16 ◽  
Author(s):  
JH Schwartz ◽  
GP Cannellos

The effect of hydroxyurea in 35 patients with chronic granulocytic leukemia (CGL), who either had entered an accelerated phase of the disease or had experienced excessive myelosuppression following alkylating agents, was studied. By either intravenous or oral administration, the drug was successful in reducing peripheral leukocyte and blast counts in all cases and in reducing splenomegaly in 13 of 17 patients. The median duration of disease control was 75 days in myeloproliferative acceleration and 27 days in frank blastic transformation. Mild nausea and vomiting were experienced by most patients, but reversible bone marrow suppression occured in only three patients. The drug proved useful in 19 patients who demonstrated myeloproliferative acceleration, especially in controlling excessive leukocytosis and/or thrombocytosis. Rapid reduction of an elevated blast cell count was achieved in nine patients who presented in blastic crisis, in an attempt to eliminate the associated risk of cerebral vascular leukostasis. Five patients who required treatment for their disease following splenectomy in the chronic phase were also well controlled. Hydroxyurea appears to have a definite role in the management of these hematologic complications of CGL.


Blood ◽  
1971 ◽  
Vol 38 (6) ◽  
pp. 671-679 ◽  
Author(s):  
GEORGE P. CANELLOS ◽  
VINCENT T. DEVITA ◽  
JACQUELINE WHANG-PENG ◽  
PAUL P. CARBONE

Abstract Thirty patients in the blastic phase of chronic granulocytic leukemia were treated with a combination of vincristine, 2.0 mg/sq m weekly, and prednisone, 60 mg/sq m orally each day. Remission was achieved in nine patients (30%), six of whom had a complete remission, and three had a good partial remission. The survival of responding patients was significantly improved over the nonresponders. Cytogenetic studies were performed on all patients in the chronic phase of the disease, and in 28 during the blastic phase. All were Philadelphia chromosome-positive throughout their course. Aneuploidy developed in 68% of the patients entering the blastic phase. Complete hematologic remission was accompanied by disappearance of aneuploid blast cell lines in the five patients in which they were detected, with return of the chromosomal constitution to that which characterized the chronic phase of their disease. Hypodiploidy in blastic transformation of CGL appeared to predict for a favorable response to vincristine and prednisone. Subsequent relapse of the disease in previously remitted patients was associated with further degrees of aneuploidy, suggesting clonal evolution of a resistant cell line.


Blood ◽  
1975 ◽  
Vol 45 (2) ◽  
pp. 197-203 ◽  
Author(s):  
GP Canellos ◽  
RC Young ◽  
PE Neiman ◽  
VT Jr DeVita

Abstract Dibromomannitol (DBM) is a new agent for the treatment of chronic granulocytic leukemia. A propsective evaluation of the drug was undertaken in a randomized comparison with busulfan. Forty previously untreated, Philadelphia chromosome-positive cases were treated, with 20 patients in each treatment group. The protocol provided for continuous maintenance therapy after remission induction, with a crossover to the opposite drug in patients who became refractory to the primary agent but are without evidence of blastic tranformation. There were 14 remissions in the DBM group and 15 in those treated with busulfan. The rate of decrease of the elevated leukocyte count was more rapid with DBM, but prolonged disease control off treatment occurred in only three of 14 cases as opposed to nine of fifteen busulfan-treated patients who required a median delay of 12 mo before maintenance could be initiated. Hypoplasia occurred in one DBM patient and two busulfan cases. Following recovery, crossover to the opposite drug in two cases again resulted in hypopllasia. Increased skin pigmentation, amenorrhea, pulmonary fibrosis, and cytologic dysplasia, commonly associated with busulfan adminstration, were also noted with DBM. The median duration of disease control with busulfan was 34 mo and 26 mo with DBM. There was no signigicant difference in the incidence of blastic transformation, and median survival for both groups was 44 mo. DBM appears to be as effective as busulfan in the treatment of the chronic phase of CGL but with a more predictable myelosuppressive action. The principal advantage of busulfan over DBM is the fact that more than half the busulfan-treated patients experienced prolonged disease control off treatment.


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