|
|
 Previous Article | Table of Contents | Next Article 
Blood, 15 November 2002, Vol. 100, No. 10, pp. 3838-3838
CORRESPONDENCE
To the editor:
Chromosome 19 abnormalities are commonly seen in AML, M7
A recent paper by Dastugue et al1 reported the
cytogenetic profile of 53 patients with acute megakaryoblastic leukemia (FAB-M7). The authors studied 30 children and 23 adults evaluated by
the Groupe Français de Cytogénétique
Hématologique, and identified 9 different groups based on their
conventional cytogenetic analysis. These groups reflect, in part, the
known association of M7 leukemia with Down syndrome, with the t(1;22)
translocation, 3q21 or q26 translocations, and with the Philadelphia
chromosome [t(9;22)]. No new recurrent abnormalities were identified,
although mapping of breakpoints identified possible rearrangement hot
spots involving 17q, 11q, 21q, and 16q. Table 1 in their manuscript showed 7 patients with trisomy 19, 1 patient with a hyperdiploid karyotype and an extra copy of chromosome 19, 1 patient with loss of
19, 1 patient with add(19)(p13), and 1 patient with a t(4;19) (p12;?) translocation. In 2001, we reported the frequent gain of chromosome 19 in
megakaryoblastic leukemias using comparative genomic hybridization (CGH).2 We used CGH and G banding to analyze both primary
patient samples and megakaryoblastic cell lines, and we found
chromosome 19 abnormalities in 4 patients by CGH that we could not
identify by G banding. Four of 12 patient samples analyzed demonstrated trisomy 19 (+19q13), with 2 of 4 acute megakaryoblastic
leukemia-M7s (AML-M7s) and 2 of 8 secondary acute leukemias,
which occurred after a myeloproliferative disorder, demonstrating this
abnormality. In addition, 9 of the 11 megakaryocytic leukemia cell
lines that we analyzed showed gain of 19 or +19q by CGH. The larger study by Dastugue et al identified an approximately 20%
incidence of chromosome 19 abnormalities with trisomy 19 occurring in 8 (16%) of 50 patients lacking the Philadelphia chromosome. The presence
of this abnormality in 8 of 9 cytogenetic subgroups suggests its
commonality in this disease process. Little emphasis was placed on this
finding in their discussion and our studies suggest that the true
incidence of trisomy (or amplification) of chromosome 19 could be even
higher, if more sensitive studies such as comparative genomic
hybridization or spectral karyotyping (SKY) are performed. This
may be especially true in the adult group, as 6 (26%) of 23 adult
patients had marker chromosomes, which could contain chromosome19
material, as we found to be the case in the M7 cell lines that we analyzed. The 19q13 region is gene rich and includes the AKT2, cyclin
E, and MLL2 genes, among others. These particular
candidate genes have been implicated in solid tumors and are under
investigation in hematologic malignancies as well. We believe the
Dastugue study provides further support for investigating the role of
chromosome 19 abnormalities in the megakaryoblastic leukemias.
Stephen D. Nimer, Donal MacGrogan, Suresh Jhanwar, and Sara Alvarez
Correspondence: Stephen D. Nimer, Memorial Sloan-Kettering
Cancer Center, 1275 York Ave, New York, NY 10021; e-mail:
s-nimer{at}mskcc.org
References
1.
Dastugue N, Lafage-Pochitaloff M, Pages MP, et al.
Cytogenetic profile of childhood and adult megakaryoblastic leukemia (M7): a study of the Groupe Francais de Cytogenetique Hematologique (GFCH).
Blood.
2002;100:618-626[Abstract/Free Full Text].
2.
Alvarez S, MacGrogan D, Calasanz MJ, Nimer SD, Jhanwar SC.
Frequent gain of chromosome 19 in megakaryoblastic leukemias detected by comparative genomic hybridization.
Genes Chromosomes Cancer.
2001;32:285-293[CrossRef][Medline]
[Order article via Infotrieve].
Response:
Common trisomies in M7
In response to our study on the cytogenetic profile of M7, Dr
Nimer et al remarked that we have not stressed the frequent gain of
chromosome 19 found in our series. Because our study was mainly based
on the search of primary changes, and because the numeric
abnormalities observed in acute myeloblastic leukemia (AML) are usually regarded as secondary changes, we have not focused our study on the numeric abnormalities. Furthermore, trisomy 19 was not found as an only (ie, a primary) change in our series. However,
abnormalities occurring during clonal evolution might also be disease
specific and help to characterize the cytogenetic profile of a
specific malignancy. To compare the frequencies of trisomy 19 in M7 and in other AMLs, we
have first estimated the relative frequencies of recurrent trisomies in
2 other large series (N.D., unpublished data,
1987-2002). One series is composed of de novo AMLs (n = 1045
cases) and another series includes only AMLs with complex karyotypes
(200 AMLs with at least 3 unrelated abnormalities) where M7 represented
1% and 2% of cases, respectively, in these 2 series. In agreement
with a previous large study on AML,1 trisomy 8 (9.5%) was
the most frequent trisomy in the de novo AML series, whereas the other trisomies were much less frequent: trisomy 21 (2.5%), trisomy 4 (2.5%), trisomy 11 (2%), and trisomy 19 (1%). In the complex karyotype series, higher frequencies of trisomies were found, but
trisomy 8 remained predominant: trisomy 8 (31%), trisomy 21 (10.5%),
trisomy 19 (9%), trisomy 11 (8%), and trisomy 4 (3%). Trisomy 19 was
the third most frequent gain. These data are in line with the frequent
occurrence of chromosome gains during clonal evolution, and chromosome
19, like chromosomes 8, 21, 11, and 4, is involved in this progression. A comparison of the above-mentioned frequencies with those reported in
our M7 series shows that, unlike in other AMLs, trisomy 8 was not
predominant in M7 and that trisomies of chromosomes 19 and 21 were the
most frequent gains. Our estimations, based on conventional cytogenetic
analyses, are therefore in agreement with a nonrandom gain of
chromosomes 19 and 21 in M7. Furthermore, as shown in Alvarez's
study,2 the frequency of these numeric changes is
probably underestimated when only conventional cytogenetics is used. We
thus agree with Dr Nimer et al that trisomy 19 also belongs to the
spectrum of nonrandom abnormalities characterizing the
megakaryoblastic proliferations.
Nicole Dastugue and Roland Berger, on behalf of the Groupe
Français de Cytogénétique Hématologique
Correspondence: Nicole Dastugue, Laboratoire
d'Hématologie, Génétique des Hémopathies,
Hôpital Purpan, 31059 Toulouse, France; e-mail:
dastugue.n{at}chu-toulouse.fr
References
1.
Grimwade D, Walker H, Oliver F, et al.
The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 Trial.
Blood.
1998;92:2322-2333[Abstract/Free Full Text].
2.
Alvarez S, MacGrogan D, Calasanz MJ, Nimer SD, Jhanwar SC.
Frequent gain of chromosome 19 in megakaryoblastic leukemias detected by comparative genomic hybridization.
Genes Chromosomes Cancer.
2001;32:285-293[CrossRef][Medline]
[Order article via Infotrieve].
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
Related Article in Blood Online:
-
Cytogenetic profile of childhood and adult megakaryoblastic leukemia (M7): a study of the Groupe Français de Cytogénétique Hématologique (GFCH)
- Nicole Dastugue, Marina Lafage-Pochitaloff, Marie-Pierre Pagès, Isabelle Radford, Christian Bastard, Pascaline Talmant, Marie Joelle Mozziconacci, Claude Léonard, Christelle Bilhou-Nabéra, Christine Cabrol, Anne-Marie Capodano, Pascale Cornillet-Lefebvre, Michel Lessard, Francine Mugneret, Christine Pérot, Sylvie Taviaux, Odile Fenneteaux, Eliane Duchayne, and Roland Berger
Blood 2002 100: 618-626.
[Abstract]
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
T. Mercher, G. Wernig, S. A. Moore, R. L. Levine, T.-L. Gu, S. Frohling, D. Cullen, R. D. Polakiewicz, O. A. Bernard, T. J. Boggon, et al.
JAK2T875N is a novel activating mutation that results in myeloproliferative disease with features of megakaryoblastic leukemia in a murine bone marrow transplantation model
Blood,
October 15, 2006;
108(8):
2770 - 2779.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Alvarez, C. Largo, D. Blesa, A. Gomez-Pineda, M. C. Martin, D. MacGrogan, J. F. Garcia, G. Roncador, J. Benitez, S. D. Nimer, et al.
Identification of Candidate Oncogenes in Acute Megakaryoblastic Leukemias with Gain of Chromosome 19.
Blood (ASH Annual Meeting Abstracts),
November 16, 2004;
104(11):
2023 - 2023.
[Abstract]
|
|
|
|
|
