Direct correlation of cytogenetic findings with cell morphology using in situ hybridization: an analysis of suspicious cells in bone marrow specimens of two patients completing therapy for acute lymphoblastic leukemia

Anastasi, John; Vardiman, JW; Rudinsky, R; Patel, Meera J.; Nachman, James B.; Cheng, Rubin; Beau, MM Le

doi:10.1182/blood.v77.11.2456.2456

Cited by 65 publications

(4 citation statements)

References 20 publications

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“…In conclusion, the study of atypical antigen combinations on leukemic cells by flow cytometry appears to be a valuable means of detecting minimal residual leukemia. We believe that it is warranted to use this approach together with other technologies (2,4,5,7,9,12,16,20,21,31,32) to get a more accurate definition of remission in acute leukemia and, consequently, develop strategies for successful clinical intervention of impending relapse.…”

Section: Discussionmentioning

confidence: 99%

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Flow cytometric determination of atypical antigen expression in acute leukemia for the study of minimal residual disease

Drach

Glassl

et al. 1992

Cytometry

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The aim of this study was to investigate to which extent acute leukemias could be monitored for residual disease by using atypical antigen combinations as leukemia-related markers. Atypical antigenic features were determined by double color flow cytometry and included coexpression of lymphoid and myeloid related antigens, unphysiological coexpression of immature and mature antigens, and lack of an antigen that is normally expressed during maturation. Atypical immunophenotypes were detected in 35 of 68 patients with AML (51.5%) and 15 of 24 patients with ALL (62.5%). When 12 patients with leukemia-associated markers were again analyzed at relapse, the relevant antigen combinations were retained in 11 of them. The sensitivity of this two color flow cytometric assay as determined in dilution experiments was 1 in lo3 to lo4 cells.Follow-up studies of bone marrow samples revealed that, after induction chemotherapy cells with leukemia-associated markers were detectable in several patients at a frequency of 0.5 to 4%, but only patients in whom the cells with atypical antigens never disappeared suffered from relapse. In contrast, patients who became negative for the atypical cells remained in complete remission (median remission duration after the first negative bone marrow assessment by flow cytometry 52 weeks, range 20-102).We conclude that atypical antigen combinations, which are present in a meaningful number of acute leukemias, are a valuable means of monitoring acute leukemia patients during follow-up. This flow cytometric approach can complement other strategies to get a more accurate definition of remission in acute leukemia. o 1992 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

“…All patients who became negative for cells with the atypical antigen combinations (pts. 2,5,8,9,[11][12][13][14] remained in complete remission. The median able (pts.…”

Section: Cells With Leukemia-associated Markers In Remission Samplesmentioning

confidence: 99%

Flow cytometric determination of atypical antigen expression in acute leukemia for the study of minimal residual disease

Drach

Glassl

et al. 1992

Cytometry

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“…Trisomy 8 is one of the most frequent chromosomal abnormalities reported in MDS.11219*20 In this study of three patients with MDS associated with trisomy 8, we have used FISH on previously stained PB smears to identify trisomic cells and to correlate the trisomic genotype with the morphologic phenotype. 16 This study has permitted us to determine the lineage of the trisomic cells, as well as to observe the response of the trisomic clone to growth-factor therapy. It has also allowed us to study the apparent expansion of the cytogenetically abnormal clone over a period of time.…”

Section: Discussionmentioning

confidence: 99%

“…The hybridization procedure was similar to that reported previously. 16 The hybridized probe was detected with fluoresceinlabeled avidin (Vector Laboratories, Burlingame, CA). An anti-fade solution was used," but no counterstain was employed.…”

Section: Control Specimensmentioning

confidence: 99%

Cytogenetic clonality in myelodysplastic syndromes studied with fluorescence in situ hybridization: lineage, response to growth factor therapy, and clone expansion

Anastasi

Feng

Beau

et al. 1993

Blood

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Clonality in myelodysplastic syndromes (MDS) has been studied with various techniques including glucose-6-phosphate dehydrogenase (G6PD) isoenzyme and cytogenetic analyses, and with molecular techniques such as gene deletion studies and the analysis of restriction fragment- length polymorphisms (RFLP) of X-linked genes. In this study, we investigated the use of fluorescence in situ hybridization (FISH) with a chromosome-specific probe to examine cytogenetic clonality in peripheral blood (PB) cells from three patients with MDS. In each case, trisomy 8 was shown by conventional cytogenetic analysis at the time of the initial diagnosis. By using FISH with a probe for the centromere of chromosome 8, we identified the trisomy in individual PB cells from Wright-stained smears. With this technique, we could determine the cell lineage involved by the trisomy, and through serial analyses we could assess the response of the clonal and nonclonal cells to growth-factor therapy, and the expansion of the trisomic clone over time. In each of the three cases, various proportions of granulocytes, monocytes, eosinophils, and basophils showed trisomy 8 by FISH analysis. In none of the cases did we detect trisomy 8 in lymphocytes. By analysis of PB cells before and during therapy with recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF), we found that GM-CSF stimulated both trisomic and disomic cells. During a 1-year period of sequential study, we detected an abrupt increase in the percentage of trisomic cells in one patient, a stable percentage in another, and a slowly increasing percentage in the third. The abrupt increase in the first patient preceded a transformation to a more acute phase by 2 months. We conclude that FISH analysis of PB cells of patients with MDS offers an additional approach to the study of clonality in this disorder. In some cases this analysis may provide a useful and simple means of assessing response to therapy and progression of disease.

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Modified interphase cytogenetics technique as an adjunct in the analysis of atypical cells in body fluids

Cajulis¹,

Gokaslan

et al. 1997

Diagn. Cytopathol.

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Our objective was to determine the value of modified interphase cytogenetics technique (MICT) by fluorescence in situ hybridization (FISH) in the study of atypical cells in body fluids in previously stained slides, allowing a direct morphologic‐cytogenetic correlation. Thirty‐five cases (29 bladder washes, four pleural fluids, two ascitic fluids) initially diagnosed as “atypical” with subsequent histologic confirmation were included. Histologically, there were 25 malignant, four dysplastic, and six benign lesions. Previously Papanicolaou or Diff‐Quick‐stained slides were marked to determine the location of the cells of interest prior to FISH analysis. A pretreatment modification using pepsin digestion was utilized. Chromosome‐specific probe 8 (Vysis) was used to detect numerical chromosomal abnormalities (NCA) involving chromosome 8. Various NCA (aneuploid) were detected in the atypical cells of histologically proven malignant cases but not in the benign cases. Using histology as a “gold standard.” FISH has a sensitivity of 83% and a specificity of 100%. In conclusion this study shows that a MICT by FISH on previously stained slides can serve as an adjunct in the study of atypical cells in body fluids. This technique allows a direct morphologic‐cytogenetic correlation which in the future may aid in the better understanding of carcinogenesis. Diagn. Cytopathol. 16:331–335, 1997. © 1997 Wiley‐Liss, Inc.

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Direct correlation of cytogenetic findings with cell morphology using in situ hybridization: an analysis of suspicious cells in bone marrow specimens of two patients completing therapy for acute lymphoblastic leukemia

Cited by 65 publications

References 20 publications

Flow cytometric determination of atypical antigen expression in acute leukemia for the study of minimal residual disease

Flow cytometric determination of atypical antigen expression in acute leukemia for the study of minimal residual disease

Cytogenetic clonality in myelodysplastic syndromes studied with fluorescence in situ hybridization: lineage, response to growth factor therapy, and clone expansion

Modified interphase cytogenetics technique as an adjunct in the analysis of atypical cells in body fluids

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