Probing the pathobiology of response to all-trans retinoic acid in acute promyelocytic leukemia: premature chromosome condensation/fluorescence in situ hybridization analysis

Blood ◽  
1996 ◽  
Vol 87 (1) ◽  
pp. 218-226 ◽  
Author(s):  
RC Vyas ◽  
SR Frankel ◽  
P Agbor ◽  
WH Jr Miller ◽  
RP Jr Warrell ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Retinoic Acid ◽  
In Situ Hybridization ◽  
Complete Remission ◽  
Fluorescence In Situ Hybridization ◽  
Bone Marrow Cells ◽  
Promyelocytic Leukemia ◽  
Premature Chromosome Condensation ◽  
Trans Retinoic Acid

Abstract The response of acute promyelocytic leukemia (APL) peripheral blood and bone marrow cells to trans-retinoic acid (RA) was cytogenetically characterized during RA treatment using the techniques of premature chromosome condensation (PCC) and fluorescence in situ hybridization (FISH). Before treatment, the predominant immature bone marrow cells were found to have t(15;17), whereas the residual mature granulocytes were diploid and lacked evidence of the translocation. In response to RA treatment, an increase in the leukocyte count was noted. The majority of these cells exhibited a t(15;17). Subsequently (eg, between days 6 and 23), 32% to 91% of the maturing myeloid cells still exhibited t(15;17). The appearance of t(15;17) in gradually maturing elements suggests that RA contributed to a release of the maturation block of the leukemic elements. As responding patients obtained complete remission, diploid elements without evidence of the translocation prevailed in the blood and bone marrow. In 16 patients studied after 1 month in complete remission, all but 2 showed all diploid cells. The residual t(15;17) cells disappeared 18 days later in 1 patient, whereas the second patient exhibited clinical evidence of relapse 20 days later. These results suggest that response of patients with APL to RA is associated with maturation, subsequent loss of the mature leukemic elements, and preferential regeneration of normal diploid hematopoietic elements.

scholarly journals Probing the pathobiology of response to all-trans retinoic acid in acute promyelocytic leukemia: premature chromosome condensation/fluorescence in situ hybridization analysis

Blood ◽  
1996 ◽  
Vol 87 (1) ◽  
pp. 218-226 ◽  
Author(s):  
RC Vyas ◽  
SR Frankel ◽  
P Agbor ◽  
WH Jr Miller ◽  
RP Jr Warrell ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Retinoic Acid ◽  
In Situ Hybridization ◽  
Complete Remission ◽  
Fluorescence In Situ Hybridization ◽  
Bone Marrow Cells ◽  
Promyelocytic Leukemia ◽  
Premature Chromosome Condensation ◽  
Trans Retinoic Acid

The response of acute promyelocytic leukemia (APL) peripheral blood and bone marrow cells to trans-retinoic acid (RA) was cytogenetically characterized during RA treatment using the techniques of premature chromosome condensation (PCC) and fluorescence in situ hybridization (FISH). Before treatment, the predominant immature bone marrow cells were found to have t(15;17), whereas the residual mature granulocytes were diploid and lacked evidence of the translocation. In response to RA treatment, an increase in the leukocyte count was noted. The majority of these cells exhibited a t(15;17). Subsequently (eg, between days 6 and 23), 32% to 91% of the maturing myeloid cells still exhibited t(15;17). The appearance of t(15;17) in gradually maturing elements suggests that RA contributed to a release of the maturation block of the leukemic elements. As responding patients obtained complete remission, diploid elements without evidence of the translocation prevailed in the blood and bone marrow. In 16 patients studied after 1 month in complete remission, all but 2 showed all diploid cells. The residual t(15;17) cells disappeared 18 days later in 1 patient, whereas the second patient exhibited clinical evidence of relapse 20 days later. These results suggest that response of patients with APL to RA is associated with maturation, subsequent loss of the mature leukemic elements, and preferential regeneration of normal diploid hematopoietic elements.

scholarly journals Detection of residual leukemic cells in patients with acute promyelocytic leukemia by the fluorescence in situ hybridization method: potential for predicting relapse

Blood ◽  
1995 ◽  
Vol 85 (2) ◽  
pp. 495-499 ◽  
Author(s):  
L Zhao ◽  
KS Chang ◽  
EH Estey ◽  
K Hayes ◽  
AB Deisseroth ◽  
...  
Keyword(s):  
Bone Marrow ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Acute Promyelocytic Leukemia ◽  
Bone Marrow Cells ◽  
Residual Disease ◽  
Promyelocytic Leukemia ◽  
Leukemic Cells ◽  
Low Frequencies

Abstract The translocation between chromosomes 15 and 17, t(15;17)(q22–24;q11– 21), is present in the bone marrow cells of most patients with acute promyelocytic leukemia (APL). Although conventional cytogenetic methods are useful for diagnosing this disease, difficulties are experienced in detecting residual disease among those patients who have achieved remission. In this study, we used the fluorescence in situ hybridization (FISH) method to attempt to detect residual leukemic cells in 10 APL patients in clinical remission. The duration of remission ranged from 2 to 93 months at the time of study. Multiple bone marrow samples were analyzed by FISH in most patients. In 6 patients, no cell with t(15;17) was found. These patients remain in complete remission at present (approximately 25 to 33 months since first studied by FISH). In 4 patients, low frequencies of cells with t(15;17) were observed in at least one bone marrow sample examined. All of these patients relapsed within 1 to 14 months. No cell with t(15;17) was identified by the conventional G-banding method in any sample. The FISH results correlated well with that of a two-round nested reverse transcription polymerase chain reaction assay that was performed on the same samples. Thus, our study suggests that FISH is potentially a useful tool for detecting residual APL cells and for identifying patients at high risk of relapse.

scholarly journals Detection of residual leukemic cells in patients with acute promyelocytic leukemia by the fluorescence in situ hybridization method: potential for predicting relapse

Blood ◽  
1995 ◽  
Vol 85 (2) ◽  
pp. 495-499
Author(s):  
L Zhao ◽  
KS Chang ◽  
EH Estey ◽  
K Hayes ◽  
AB Deisseroth ◽  
...  
Keyword(s):  
Bone Marrow ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Acute Promyelocytic Leukemia ◽  
Bone Marrow Cells ◽  
Residual Disease ◽  
Promyelocytic Leukemia ◽  
Leukemic Cells ◽  
Low Frequencies

The translocation between chromosomes 15 and 17, t(15;17)(q22–24;q11– 21), is present in the bone marrow cells of most patients with acute promyelocytic leukemia (APL). Although conventional cytogenetic methods are useful for diagnosing this disease, difficulties are experienced in detecting residual disease among those patients who have achieved remission. In this study, we used the fluorescence in situ hybridization (FISH) method to attempt to detect residual leukemic cells in 10 APL patients in clinical remission. The duration of remission ranged from 2 to 93 months at the time of study. Multiple bone marrow samples were analyzed by FISH in most patients. In 6 patients, no cell with t(15;17) was found. These patients remain in complete remission at present (approximately 25 to 33 months since first studied by FISH). In 4 patients, low frequencies of cells with t(15;17) were observed in at least one bone marrow sample examined. All of these patients relapsed within 1 to 14 months. No cell with t(15;17) was identified by the conventional G-banding method in any sample. The FISH results correlated well with that of a two-round nested reverse transcription polymerase chain reaction assay that was performed on the same samples. Thus, our study suggests that FISH is potentially a useful tool for detecting residual APL cells and for identifying patients at high risk of relapse.

Study On the Clonal Origin of Dysplastic Cells by Fluorescence in Situ Hybridization in Myelodysplastic Syndromes.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4858-4858
Author(s):  
Jun Zhang ◽  
Yongquan Xue ◽  
Jinlan Pan ◽  
Yafang Wu ◽  
Juan Shen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Myelodysplastic Syndromes ◽  
Chromosomal Abnormalities ◽  
Bone Marrow Cells ◽  
Conflicts Of Interest ◽  
Banding Technique ◽  
Clonal Origin

Abstract Abstract 4858 Objective To determining the clonal origin of dysplatic cells in Myelodysplastic syndromes (MDS) . Methods Karyotypic analyses of bone marrow cells using R-banding technique were carried out to determine the chromosomal abnormalities. Interphase fluorescence in situ hybridization (FISH) and morphologic analysis of bone marrow aspirates were performed in the same cells to investigate the clonal origin of dysplatic cells in 8 MDS patients. Result All patients had clonal karyotypic abnormalities: simple abnormality in 1 patient, complex abnormalities in 6 patients, coexistent of two unrelated clones in 1 patient. Most of dysplastic cells in 7 of 8 MDS patients derived from neoplasia clone while 1 patient had a reverse result,no matter what cell lineage was involved. Some of non-dysplastic cells of all patients derived from malignant clone; in 7 patients, the proportion of dysplastic cells in malignant clone were significantly higher than that of non- malignant clone. Conclusion Most of dysplastic cells in MDS derived from malignant clones, while the minority of them derived from non-malignant clones. Thus, it is reasonable to expect that in most cases myelodysplasia is present in malignant clone and can be taken as an important diagnostic evidence for MDS. Disclosures No relevant conflicts of interest to declare.

scholarly journals Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 567-572 ◽  
Author(s):  
ME Huang ◽  
YC Ye ◽  
SR Chen ◽  
JR Chai ◽  
JX Lu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Retinoic Acid ◽  
Complete Remission ◽  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Nitroblue Tetrazolium Reduction ◽  
Morphological Maturation

Twenty-four patients with acute promyelocytic leukemia (APL) were treated with all-trans retinoic acid (45 to 100 mg/m2/day). Of these, eight cases had been either nonresponsive or resistant to previous chemotherapy; the other 16 cases were previously untreated. All patients attained complete remission without developing bone marrow hypoplasia. Bone marrow suspension cultures were studied in 15 of the 24 patients. Fourteen of these patients had morphological maturation in response to the retinoic acid (1 mumol/L). Chloroacetate esterase and alpha-naphthyl acetate esterase staining as well as electronmicroscopic examination confirmed that retinoic acid-induced cells differentiated to granulocytes with increased functional maturation (as measured by nitroblue tetrazolium reduction, NBT). The single nonresponder to retinoic acid in vitro was resistant to treatment with retinoic acid but attained complete remission after addition of low-dose cytosine arabinoside (ara-C). During the course of therapy, none of the patients showed any abnormalities in the coagulation parameters we measured, suggesting an absence of any subclinical disseminated intravascular coagulation. The only side effects consisted of mild dryness of the lips and skin, with occasional headaches and digestive symptoms. Eight patients have relapsed after 2 to 5 months of complete remission. The others remain in complete remission at 1+ to 11+ months and are still being followed up. We conclude that all-trans retinoic acid is an effective inducer for attaining complete remission in APL.

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