Cytogenetic and clinical investigations in 76 cases with therapy-related leukemia and myelodysplastic syndrome

Iurlo, Alessandra; Mecucci, Cristina; Orshoven, Angeline Van; Michaux, Jean Louis; Boogaerts, Marc; Noens, Lucien; Bosly, André; Louwagie, A.; Berghe, Herman Van den

doi:10.1016/0165-4608(89)90034-4

Cited by 68 publications

(29 citation statements)

References 22 publications

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“…The associations observed between type of prior CT/RT and cytogenetic abnormalities fit well with previous reports, although there are some conflicting data as regards possible associations between prior RT and 5q−. 4,8,45,47,52 In fact, the leukemogenic role of RT as well as the impact of RT on type of cytogenetic abnormalities in t-AML/t-MDS have been debated quite extensively. [53][54][55][56] It is noteworthy that the frequencies of some abnormalities, although being significantly higher in t-AML and/or t-MDS, did not vary significantly among the treatment groups (Tables 2 and 3).…”

Section: Discussionsupporting

confidence: 76%

“…In the majority of other reports, the percentages of previous non-neoplastic diseases have generally been lower, varying from 2 to 13%. [6][7][8][9]16,19,[44][45][46][47][48][49][50] The pooled analysis of the cytogenetic features of t-AML/t-MDS, including data from unselected series in the literature, 32 revealed several significant differences between treatmentrelated and de novo disorders (Tables 2 and 3). In t-AML/t-MDS, the number of anomalies and the ploidy levels differed from de novo cases, with complex karyotypes and hypodiploidy being more common in t-AML/t-MDS.…”

Section: Discussionmentioning

confidence: 99%

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Pooled analysis of clinical and cytogenetic features in treatment-related and de novo adult acute myeloid leukemia and myelodysplastic syndromes based on a consecutive series of 761 patients analyzed 1976–1993 and on 5098 unselected cases reported in the literature 1974–2001

et al. 2002

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To ascertain the frequency of treatment-related acute myeloid leukemias and myelodysplastic syndromes (t-AML/t-MDS) in an unselected series, we have identified all adult cases analyzed in our department from 1976 to 1993. Further aims were to compare karyotypic features of t-AML/t-MDS with de novo AML/MDS, in our material as well as in 5098 unselected, cytogenetically abnormal, published cases, and to analyze associations between type of prior therapy and karyotype. Among our 372 AML and 389 MDS, 47 (13%) were t-AML and 62 (16%) were t-MDS. Clonal abnormalities were significantly more common in t-AML and t-MDS than in de novo disease (68% vs 50%, P Ͻ 0.05 and 84% vs 45%, P Ͻ 0.001, respectively). Among the available 4230 AML and 1629 MDS (the present series and published cases), 14% were t-AML and 15% were t-MDS. In t-AML/t-MDS, the number of anomalies and the ploidy levels differed significantly from de novo cases, with complex and hypodiploid karyotypes being more common in t-AML/t-MDS. In t-AML, unbalanced changes in general, t(1;3), der(1;7), 3p−, −5, 5q−, −7, 7q−, t(9;11), t(11;19), t(11q23), der(12p), −17, der(17p), −18, and −21 were significantly more frequent than in de novo AML. In t-MDS, −5, −7, 7q−, 13q−, der(17p), and −18 were significantly more common. Type of prior treatment correlated significantly with number of anomalies in t-AML and with ploidy levels in t-AML/t-MDS. The frequencies of several aberrations varied with type of therapy, eg, 5q− was more frequent in radiotherapyassociated t-MDS, monosomy 7 was more common in t-AML and t-MDS after treatment with alkylators, and t(11q23) in t-AML was associated with topoisomerase II inhibitors. Abnormalities significantly more common in de novo disease were +8 as a sole anomaly, balanced changes in general, t(8;21), t(9;22), t(15;17), inv(16), and t(21q22) in AML, and −Y, 5q−, and 20q− as sole anomalies and +8 in MDS. The results emphasize the strong association between previous genotoxic exposure and karyotypic features. Leukemia (2002) IntroductionEver since the mid-1970s, when the first case reports describing chromosomal abnormalities in treatment-related acute myeloid leukemias (t-AML) were published, 1,2 the cytogenetic features of t-AML and of therapy-associated myelodysplastic syndromes (t-MDS) have received much attention. 3,4 To date, two distinct karyotypic patterns that correlate with specific types of chemotherapeutic agents have emerged. Previous chemotherapy (CT) with alkylators (alk) has been strongly linked to the development of t-MDS/t-AML harboring unbal- anced changes, mainly whole or partial losses of chromosomes 5 and 7, often in complex, hypodiploid karyotypes, 5-9 whereas prior CT with DNA topoisomerase II inhibitors (topo II) has been associated with t-AML characterized by, in particular, translocations involving chromosome band 11q23 resulting in MLL gene rearrangements. 4,[10][11][12] It has been debated, but remains to be settled, whether prior radiotherapy (RT) alone or exposure to CT other than alk/topo II may correla...

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Pooled analysis of clinical and cytogenetic features in treatment-related and de novo adult acute myeloid leukemia and myelodysplastic syndromes based on a consecutive series of 761 patients analyzed 1976–1993 and on 5098 unselected cases reported in the literature 1974–2001

et al. 2002

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“…[11][12][13][14][15][16][17][18][19][20][21][22][23][24] More recently, the DNA topoisomerase II inhibitors have also been shown to be leukemogenic, in most instances administered in combination with platinum derivatives or an alkylating agent. [25][26][27][28] These leukemias primarily present balanced translocations to chromosome bands 11q23 or 21q22 29 with rearrangement of the MLL and the AML1 genes, but also less frequently other balanced rearrangements such as the inv (16)(p13q22), and the t(15;17)(q22;q11) known from de novo MDS and AML.…”

Section: Discussionmentioning

confidence: 99%

“…Alternatively, the formation of a dicentric chromosome containing 1q could precede and perhaps predispose to a subsequent duplication of the whole chromosome. Trisomy for chromosome 1, however, is an uncommon cytogenetic finding in t-MDS and t-AML, [14][15][16][17][18][19][20][21][22][23][24] and the presence of dicentrics apparently does not result in duplication of other chromosomes or parts of chromosomes, except for 1q and the involved arms of the isodicentric chromosomes.…”

Section: Tablementioning

confidence: 99%

Increased frequency of dicentric chromosomes in therapy-related MDS and AML compared to de novo disease is significantly related to previous treatment with alkylating agents and suggests a specific susceptibility to chromosome breakage at the centromere

Andersen

Pedersen‐Bjergaard

2000

Leukemia

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Dicentric chromosomes are observed in many malignant diseases including myelodysplasia (MDS) and acute myeloid leukemia (AML) and have often been observed in a subset of these diseases, namely therapy-related MDS (t-MDS) and AML (t-AML). Using fluorescence in situ hybridization (FISH) with centromere-specific probes, we investigated the frequency and type of dicentric chromosomes in 180 consecutive patients with t-MDS and t-AML and in 231 consecutive patients with de novo MDS and AML, whose karyotypes had been studied previously by conventional G-banding. Twenty-seven out of 180 patients with t-MDS or t-AML presented dicentric chromosomes compared to only seven out of 231 patients with de novo disease (P = 0.00003). A dic(1q;7p) was observed in 10 cases, a dic(5p;17q) was observed in six cases, whereas various isodicentric chromosomes were observed in six cases. Excluding these six cases with isodicentrics, all 25 patients with dicentric chromosomes had involvement of at least one of the chromosome arms 1q, 5p, or 7p resulting in monosomy for 5q or 7q, and/or trisomy for 1q. Patients with dicentric chromosomes presented significantly more often as t-MDS compared to patients without dicentrics (P = 0.046), and the presence of a dicentric chromosome was significantly related to previous therapy with alkylating agents (P = 0.026). Thus, only one out of 27 patients with a dicentric chromosome had not previously received an alkylating agent. A specific susceptibility to breakage at the centromere after exposure to alkylating agents is suggested and may explain the frequent loss of whole chromosomes, in particular chromosomes 5 and 7 in t-MDS and t-AML, if the breaks are not followed by rejoining. Leukemia (2000) 14, 105-111.

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“…In contrast to the case reports described above, several large-scale leukemia studies have been conducted that surveyed their subjects for information on prior chemical exposures (Cuneo et al, 1992;Golomb et al, 1982;Groupe, 1984;Iurlo et al, 1989;Li et al, 1989;Mitelman et al, 1978;Mitelman et al, 1981;Richardson et al, 1992). These studies compared chromosome changes in leukemia patients with various occupational chemical exposures and in those without exposure.…”

Section: F Chromosome Changes In Leukemia Patients With Likely Priormentioning

confidence: 99%

The Nature of Chromosomal Aberrations Detected in Humans Exposed to Benzene

Zhang¹,

Eastmond

Smith³

2002

Critical Reviews in Toxicology

151

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Cytogenetic and clinical investigations in 76 cases with therapy-related leukemia and myelodysplastic syndrome

Cited by 68 publications

References 22 publications

Pooled analysis of clinical and cytogenetic features in treatment-related and de novo adult acute myeloid leukemia and myelodysplastic syndromes based on a consecutive series of 761 patients analyzed 1976–1993 and on 5098 unselected cases reported in the literature 1974–2001

Pooled analysis of clinical and cytogenetic features in treatment-related and de novo adult acute myeloid leukemia and myelodysplastic syndromes based on a consecutive series of 761 patients analyzed 1976–1993 and on 5098 unselected cases reported in the literature 1974–2001

Increased frequency of dicentric chromosomes in therapy-related MDS and AML compared to de novo disease is significantly related to previous treatment with alkylating agents and suggests a specific susceptibility to chromosome breakage at the centromere

The Nature of Chromosomal Aberrations Detected in Humans Exposed to Benzene

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