scholarly journals Clonal analysis of basophil differentiation in bone marrow cultures from a Down's syndrome patient with megakaryoblastic leukemia

Blood ◽  
1985 ◽  
Vol 66 (6) ◽  
pp. 1278-1283
Author(s):  
T Suda ◽  
J Suda ◽  
Y Miura ◽  
Y Hayashi ◽  
M Eguchi ◽  
...  

We present the in vitro differentiation of marrow cells from a patient with Down's syndrome accompanied by megakaryoblastic leukemia into basophils in the presence of phytohemagglutinin-stimulated leukocyte conditioned medium, using a liquid culture and methylcellulose culture system. Identification of basophils was established by metachromatic staining with toluidine blue, transmission electron microscopy, and the presence of histamine. However, these basophils did not release histamine in response to calcium ionophore or chemotactic peptide. Samples from suspension cultures that contained 90% basophils showed chromosomal markers characteristic of leukemic cells (48, XY, +11, +21, t(1;15)) in all examined mitoses. The cellular composition of leukemic colonies grown in methylcellulose culture from single cells was studied using the micromanipulation technique. High plating efficiency and extreme predominance of basophil colonies were observed. In a total 137 cultures, 79 revealed colony growth. Of 59 colonies that were analyzed by cytologic examination, 46 were pure basophil colonies. These basophil colonies showed disperse morphology, similar to that of a normal basophil colony. The clonality of the basophil colonies and skewing of lineage expression were documented from leukemic single-cell cultures. These data showed that leukemic cells have the capacity for differentiation into some lineages that are not expressed in vivo.

Blood ◽  
1985 ◽  
Vol 66 (6) ◽  
pp. 1278-1283 ◽  
Author(s):  
T Suda ◽  
J Suda ◽  
Y Miura ◽  
Y Hayashi ◽  
M Eguchi ◽  
...  

Abstract We present the in vitro differentiation of marrow cells from a patient with Down's syndrome accompanied by megakaryoblastic leukemia into basophils in the presence of phytohemagglutinin-stimulated leukocyte conditioned medium, using a liquid culture and methylcellulose culture system. Identification of basophils was established by metachromatic staining with toluidine blue, transmission electron microscopy, and the presence of histamine. However, these basophils did not release histamine in response to calcium ionophore or chemotactic peptide. Samples from suspension cultures that contained 90% basophils showed chromosomal markers characteristic of leukemic cells (48, XY, +11, +21, t(1;15)) in all examined mitoses. The cellular composition of leukemic colonies grown in methylcellulose culture from single cells was studied using the micromanipulation technique. High plating efficiency and extreme predominance of basophil colonies were observed. In a total 137 cultures, 79 revealed colony growth. Of 59 colonies that were analyzed by cytologic examination, 46 were pure basophil colonies. These basophil colonies showed disperse morphology, similar to that of a normal basophil colony. The clonality of the basophil colonies and skewing of lineage expression were documented from leukemic single-cell cultures. These data showed that leukemic cells have the capacity for differentiation into some lineages that are not expressed in vivo.


Blood ◽  
1987 ◽  
Vol 69 (2) ◽  
pp. 508-512
Author(s):  
J Suda ◽  
M Eguchi ◽  
Y Akiyama ◽  
Y Iwama ◽  
T Furukawa ◽  
...  

A male neonate with Down's syndrome and congenital myeloproliferative disorder was studied. His blood picture showed the unique coexistence of leukocytosis with matured cells and a large number of blast cells. The in vitro proliferation and differentiation of blast cells into various lineages in the presence of phytohemagglutinin-stimulated leukocyte conditioned medium (PHA-LCM) was examined by using a liquid culture and a methylcellulose culture system. The differentiation of blast cells into myeloid cells was confirmed by specific cytochemical stainings, electron microscopy, and an immunologic study. No specific factors in the plasma of the patient promoted the proliferation or differentiation of blast cells. The cellular composition of colonies grown in methylcellulose culture from single blast cells was studied by a micromanipulation technique. High plating efficiency was observed. Of 136 cultures, 78 showed colony growth. Half of the blast cells were colony-forming cells that could proliferate and differentiate into basophils, neutrophils, eosinophils, macrophages, and erythrocytes in the presence of PHA-LCM. Using the blast cells with a high differentiation capacity to the basophil pathway, we studied the effect of recombinant granulocyte-macrophage colony-stimulating factor (GM- CSF). Recombinant GM-CSF support neutrophils, eosinophils, and macrophages but not typical basophils. These findings of the cell differentiation of blast cells into various kinds of cells in vitro were in agreement with the finding of neutrophilia, eosinophilia, basophilia, and thrombocythemia in this patient.


Blood ◽  
1987 ◽  
Vol 69 (2) ◽  
pp. 508-512 ◽  
Author(s):  
J Suda ◽  
M Eguchi ◽  
Y Akiyama ◽  
Y Iwama ◽  
T Furukawa ◽  
...  

Abstract A male neonate with Down's syndrome and congenital myeloproliferative disorder was studied. His blood picture showed the unique coexistence of leukocytosis with matured cells and a large number of blast cells. The in vitro proliferation and differentiation of blast cells into various lineages in the presence of phytohemagglutinin-stimulated leukocyte conditioned medium (PHA-LCM) was examined by using a liquid culture and a methylcellulose culture system. The differentiation of blast cells into myeloid cells was confirmed by specific cytochemical stainings, electron microscopy, and an immunologic study. No specific factors in the plasma of the patient promoted the proliferation or differentiation of blast cells. The cellular composition of colonies grown in methylcellulose culture from single blast cells was studied by a micromanipulation technique. High plating efficiency was observed. Of 136 cultures, 78 showed colony growth. Half of the blast cells were colony-forming cells that could proliferate and differentiate into basophils, neutrophils, eosinophils, macrophages, and erythrocytes in the presence of PHA-LCM. Using the blast cells with a high differentiation capacity to the basophil pathway, we studied the effect of recombinant granulocyte-macrophage colony-stimulating factor (GM- CSF). Recombinant GM-CSF support neutrophils, eosinophils, and macrophages but not typical basophils. These findings of the cell differentiation of blast cells into various kinds of cells in vitro were in agreement with the finding of neutrophilia, eosinophilia, basophilia, and thrombocythemia in this patient.


Blood ◽  
1991 ◽  
Vol 77 (12) ◽  
pp. 2569-2576 ◽  
Author(s):  
T Papayannopoulou ◽  
B Nakamoto ◽  
NP Anagnou ◽  
D Chui ◽  
L Dow ◽  
...  

Abstract Juvenile chronic myelocytic leukemia (JCML) is a rare hematopoietic neoplasia of early childhood with distinct hematologic and biochemical features. We studied the biologic properties and the globin synthetic profiles of JCML erythroid cells both in vivo and in vitro from a total of 24 patients. In these cases we observed the exuberant colony-forming unit-macrophage (CFU-M) colony growth, as reported previously. Furthermore, in contrast to previous reports, we found significant erythroid colony growth in most of our cases (average: 1,182 burst- forming unit-erythroid [BFUe] per 10(5) plated cells, range: 40 to 6,927). This growth was by and large erythropoietin-dependent and was not greatly influenced by other added cytokines. By several criteria all erythroid colony growth detected in vitro was derived from JCML progenitors. The globin synthetic profile of JCML erythroid cells showed high levels of fetal hemoglobin both in vivo and in vitro (gamma/gamma + beta: 53% to 94% in reticulocytes, 62% to 98% in BFUe- derived cells). In addition (in seven cases studied) we detected embryonic globins (epsilon and zeta) at the protein and messenger RNA level, a novel finding for primary leukemic cells. We speculate that the transformed erythroid cells in JCML harbor a trans environment supporting expression of developmentally earlier genes (fetal, embryonic). However, in contrast to other acute or subacute leukemias, JCML erythroid cells also have the ability to reach full maturation to the red cell level, thus allowing detection of this primitive program in vivo.


Blood ◽  
1991 ◽  
Vol 77 (12) ◽  
pp. 2569-2576 ◽  
Author(s):  
T Papayannopoulou ◽  
B Nakamoto ◽  
NP Anagnou ◽  
D Chui ◽  
L Dow ◽  
...  

Juvenile chronic myelocytic leukemia (JCML) is a rare hematopoietic neoplasia of early childhood with distinct hematologic and biochemical features. We studied the biologic properties and the globin synthetic profiles of JCML erythroid cells both in vivo and in vitro from a total of 24 patients. In these cases we observed the exuberant colony-forming unit-macrophage (CFU-M) colony growth, as reported previously. Furthermore, in contrast to previous reports, we found significant erythroid colony growth in most of our cases (average: 1,182 burst- forming unit-erythroid [BFUe] per 10(5) plated cells, range: 40 to 6,927). This growth was by and large erythropoietin-dependent and was not greatly influenced by other added cytokines. By several criteria all erythroid colony growth detected in vitro was derived from JCML progenitors. The globin synthetic profile of JCML erythroid cells showed high levels of fetal hemoglobin both in vivo and in vitro (gamma/gamma + beta: 53% to 94% in reticulocytes, 62% to 98% in BFUe- derived cells). In addition (in seven cases studied) we detected embryonic globins (epsilon and zeta) at the protein and messenger RNA level, a novel finding for primary leukemic cells. We speculate that the transformed erythroid cells in JCML harbor a trans environment supporting expression of developmentally earlier genes (fetal, embryonic). However, in contrast to other acute or subacute leukemias, JCML erythroid cells also have the ability to reach full maturation to the red cell level, thus allowing detection of this primitive program in vivo.


2021 ◽  
Vol 64 (1) ◽  
Author(s):  
Senthil Nagarajan ◽  
Jae Kwon Lee

AbstractSesamolin is one of the lignans derived from sesame oil. It has demonstrated significant antioxidant, anti-aging, and anti-mutagenic properties. It also reportedly augments natural killer (NK) cell lysis activity. We previously reported that sesamolin also exerts anticancer effects in vitro and induces enhanced NK cell cytolytic activity against tumor cells. Herein, we aimed to determine the mechanism by which sesamolin prevents and retards tumorigenesis in BALB/c mouse models of leukemia induced by murine (BALB/c) myelomonocytic leukemia WEHI-3B cells. Banded neutrophils, myeloblasts, and monocytic leukemic cells were more abundant in the leukemia model than in normal mice. Sesamolin decreased the number of leukemic cells by almost 60% in the leukemia model mice in vivo; additionally, sesamolin and the positive control drug, vinblastine, similarly hindered neoplastic cell proliferation. Spleen samples were ~ 4.5-fold heavier in leukemic mice than those obtained from normal mice, whereas spleen samples obtained from leukemic mice treated with sesamolin had a similar weight to those of normal mice. Moreover, sesamolin induced a twofold increase in the cytotoxic activity of leukemic mouse NK cells against WEHI-3B cells. These results indicated that sesamolin exerts anti-leukemic effects in vivo.


2000 ◽  
Vol 48 (5) ◽  
pp. 795-798 ◽  
Author(s):  
Domenico Pratic� ◽  
Luigi Iuliano ◽  
Giulia Amerio ◽  
Lina X. Tang ◽  
Joshua Rokach ◽  
...  

Blood ◽  
2001 ◽  
Vol 98 (9) ◽  
pp. 2862-2864 ◽  
Author(s):  
Bruno Cassinat ◽  
Sylvie Chevret ◽  
Fabien Zassadowski ◽  
Nicole Balitrand ◽  
Isabelle Guillemot ◽  
...  

Abstract Acute promyelocytic leukemia (APL) blasts possess a unique sensitivity to the differentiating effects of all-transretinoic acid (ATRA). Multicenter trials confirm that the combination of differentiation and cytotoxic therapy prolongs survival in APL patients. However relapses still occur, and exquisite adaptation of therapy to prognostic factors is essential to aim at a possible cure of the disease. A heterogeneity was previously reported in the differentiation rate of patients' APL blasts, and it was postulated that this may reflect the in vivo heterogeneous outcome. In this study, it is demonstrated that patients of the APL93 trial whose leukemic cells achieved optimal differentiation with ATRA in vitro at diagnosis had a significantly improved event-free survival (P = .01) and lower relapse rate (P = .04). This analysis highlights the importance of the differentiation step in APL therapy and justifies ongoing studies aimed at identifying novel RA-differentiation enhancers.


Plant Disease ◽  
2008 ◽  
Vol 92 (10) ◽  
pp. 1439-1443 ◽  
Author(s):  
Adalberto C. Café-Filho ◽  
Jean Beagle Ristaino

Despite the wide adoption of mefenoxam (Ridomil Gold EC) for vegetables in North Carolina, the incidence of Phytophthora blight on pepper (Capsicum annuum) and squash (Cucurbita pepo) is high. Seventy-five isolates of Phytophthora capsici were collected in five pepper and one squash field in order to assess mefenoxam sensitivity. The relative fitness of resistant and sensitive isolates was contrasted in vitro by their respective rates of colony growth and their ability to produce sporangia in unamended V8 juice agar medium. In in vivo experiments, the aggressiveness of isolates on pepper was evaluated. The frequency of resistant isolates in North Carolina populations was 63%, considerably higher than resistance levels in areas where mefenoxam is not widely adopted. Resistant isolates grew on amended media at rates >80 to 90% and >100% of the nonamended control at 100 μg ml-1 and 5 μg ml-1, respectively. Sensitive isolates did not growth at 5 or 100 μg ml-1. All isolates from three fields, including two pepper and a squash field, were resistant to mefenoxam. Populations from other fields were composed of either mixes of sensitive and resistant isolates or only sensitive isolates. Response to mefenoxam remained stable during the course of in vitro and in planta experiments. Occurrence of a mefenoxam-resistant population of P. capsici on squash is reported here for the first time in North Carolina. When measured by rate of colony growth, sporulation in vitro, or aggressiveness in planta, fitness of resistant isolates was not reduced. Mefenoxam-resistant isolates from squash were as aggressive on pepper as sensitive or resistant pepper isolates. These results suggest that mefenoxam-resistant populations of P. capsici are as virulent and fit as sensitive populations.


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