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Minimal residual disease and trisomy 8
Cancer Genetics and Cytogenetics 140 (2003) 176
Letter to the editor
Minimal residual disease and trisomy 8 We read with interest the communication by Scaravaglio et al. [1] concerning the detection of minimal residual disease (MRD) by fluorescence in situ hybridization (FISH) analysis on interphase nuclei in peripheral blood stem cells used for autologous bone marrow transplantation (ABMT) in two patients with acute myelocytic leukemia (AML) characterized by trisomy 8. Our keen interest was due to the fact that we pointed out several years ago the possibility that cytogenetic data might be instrumental to detect MRD in view of ABMT [2], and also to the fact that we have been studying trisomy 8 in AML and myelodysplastic syndromes (MDS) in various respects for many years. We agree with the general conclusions reached by the authors, but two points deserve a comment. The first one concerns the analysis of the interphase FISH results: the data concerning nuclei with three signals in the patients’ samples are considered significantly higher than controls when exceeding the mean of these 3 SD [1]. Only percentages are offered in the paper [1]: so we tried to reconstruct raw numbers and found that the number of trisomic nuclei in the patients’ samples were 10–22 out of 509–607. As to the six controls, the number of nuclei scored is claimed to be between 500 and 820, that is a mean of 660: raw numbers of trisomic nuclei would therefore be from 1 to 5–6 (with the exception of one control with no trisomic cell). A statistical treatment of these data is not possible, and usual statistic comparisons between means are not reliable with such small numbers [3]. So, we feel that MRD was in fact suggested, but not demonstrated beyond any reasonable doubt by the interphase FISH data obtained. The clinical course subsequent to ABMT confirmed MRD, but it is necessary to be cautious in the interpretation of such kind of data.
Secondly, we remark again that the association of MRD detection with poor prognosis after ABMT is indicated in the two patients reported by the early relapse that took place. However, we demonstrated recently that a proportion not lower than 15%– 20% of MDS/AML cases with a trisomy 8, which is interpreted as acquired, are in fact constitutional trisomy 8 mosaics, in whom the MDS/AML clone arose from a trisomic cell [4]. This fact should also be taken into account to interpret nuclei FISH data in relation to MRD in patients with an apparently acquired trisomy 8. Francesco Pasquali1 Emanuela Maserati Dipartimento di Scienze Biomediche Sperimentali e Cliniche Università dell’Insubria Via J.H. Dunant, 5 21100 Varese, Italy
References [1] Scaravaglio P, Guglielmelli T, Giugliano E, Marmont F, Audisio E, Gallo E, Saglio G, Rege-Cambrin G. Detection of minimal residual disease in peripheral blood stem cells from two acute myeloid leukemia patients with trisomy 8 predicts early relapse after autologous bone marrow transplantation. Cancer Genet Cytogenet 2002;133:98–101. [2] Maserati E, Campagnoli E, Truglio F, Porta F, Nespoli L, Burgio GR, Pasquali F. Cytogenetics in autologous bone marrow transplantation. Cancer Genet Cytogenet 1990;45:137–8. [3] Smith CAB. Chi-squared tests with small numbers. Ann Hum Genet 1986;50:163–7. [4] Maserati E, Aprili F, Vinante F, Locatelli F, Amendola G, Zatterale A, Milone G, Minelli A, Bernardi F, Lo Curto F, Pasquali F. Trisomy 8 in myelodysplasia and acute leukemia is constitutional in 15–20% of cases. Genes Chromosomes Cancer 2002;33:93–7.
Tel.: 39-0332-217180; fax: 39-0332-217119. E-mail address: [email protected].
1
0165-4608/03/$ – see front matter © 2003 Elsevier Science Inc. All rights reserved. PII: S0165-4608(02)00 6 7 9 - 9
Letter to the editor
Minimal residual disease and trisomy 8 We read with interest the communication by Scaravaglio et al. [1] concerning the detection of minimal residual disease (MRD) by fluorescence in situ hybridization (FISH) analysis on interphase nuclei in peripheral blood stem cells used for autologous bone marrow transplantation (ABMT) in two patients with acute myelocytic leukemia (AML) characterized by trisomy 8. Our keen interest was due to the fact that we pointed out several years ago the possibility that cytogenetic data might be instrumental to detect MRD in view of ABMT [2], and also to the fact that we have been studying trisomy 8 in AML and myelodysplastic syndromes (MDS) in various respects for many years. We agree with the general conclusions reached by the authors, but two points deserve a comment. The first one concerns the analysis of the interphase FISH results: the data concerning nuclei with three signals in the patients’ samples are considered significantly higher than controls when exceeding the mean of these 3 SD [1]. Only percentages are offered in the paper [1]: so we tried to reconstruct raw numbers and found that the number of trisomic nuclei in the patients’ samples were 10–22 out of 509–607. As to the six controls, the number of nuclei scored is claimed to be between 500 and 820, that is a mean of 660: raw numbers of trisomic nuclei would therefore be from 1 to 5–6 (with the exception of one control with no trisomic cell). A statistical treatment of these data is not possible, and usual statistic comparisons between means are not reliable with such small numbers [3]. So, we feel that MRD was in fact suggested, but not demonstrated beyond any reasonable doubt by the interphase FISH data obtained. The clinical course subsequent to ABMT confirmed MRD, but it is necessary to be cautious in the interpretation of such kind of data.
Secondly, we remark again that the association of MRD detection with poor prognosis after ABMT is indicated in the two patients reported by the early relapse that took place. However, we demonstrated recently that a proportion not lower than 15%– 20% of MDS/AML cases with a trisomy 8, which is interpreted as acquired, are in fact constitutional trisomy 8 mosaics, in whom the MDS/AML clone arose from a trisomic cell [4]. This fact should also be taken into account to interpret nuclei FISH data in relation to MRD in patients with an apparently acquired trisomy 8. Francesco Pasquali1 Emanuela Maserati Dipartimento di Scienze Biomediche Sperimentali e Cliniche Università dell’Insubria Via J.H. Dunant, 5 21100 Varese, Italy
References [1] Scaravaglio P, Guglielmelli T, Giugliano E, Marmont F, Audisio E, Gallo E, Saglio G, Rege-Cambrin G. Detection of minimal residual disease in peripheral blood stem cells from two acute myeloid leukemia patients with trisomy 8 predicts early relapse after autologous bone marrow transplantation. Cancer Genet Cytogenet 2002;133:98–101. [2] Maserati E, Campagnoli E, Truglio F, Porta F, Nespoli L, Burgio GR, Pasquali F. Cytogenetics in autologous bone marrow transplantation. Cancer Genet Cytogenet 1990;45:137–8. [3] Smith CAB. Chi-squared tests with small numbers. Ann Hum Genet 1986;50:163–7. [4] Maserati E, Aprili F, Vinante F, Locatelli F, Amendola G, Zatterale A, Milone G, Minelli A, Bernardi F, Lo Curto F, Pasquali F. Trisomy 8 in myelodysplasia and acute leukemia is constitutional in 15–20% of cases. Genes Chromosomes Cancer 2002;33:93–7.
Tel.: 39-0332-217180; fax: 39-0332-217119. E-mail address: [email protected].
1
0165-4608/03/$ – see front matter © 2003 Elsevier Science Inc. All rights reserved. PII: S0165-4608(02)00 6 7 9 - 9