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T Fioretos

Publications and source records attributed to T Fioretos.

At least 19 recordsLinked to original sources
PubMed2007

Cytogenetic evolution patterns in CML post-SCT.

The cytogenetic evolution patterns in chronic myeloid leukemia (CML) after allogeneic (allo) stem cell transplantation (SCT) are different from the ones observed in non-transplanted patients, a phenomenon suggested to be caused by the conditioning regime. We reviewed 131 CMLs displaying karyotypic evolution after SCT (122 allo, nine autologous (auto)), treated at Lund University Hospital or reported in the literature. Major route abnormalities (i.e., +8, +Ph, i(17q), +19, +21, +17 and -7) were seen in 14%, balanced aberrations in 61%, hyperdiploidy in 19%, pseudodiploidy in 79%, divergent clones in 14%, and Ph-negative clones in 21%. The breakpoints involved in secondary structural rearrangements clustered at 1q21, 1q32, 7q22, 9q34, 11q13, 11q23, 12q24, 13q14, 17q10 and 22q11. Cytogenetic abnormalities common in AML after genotoxic exposure, that is, der(1;7)(q10;p10), del(3p), -5, del(5q), -7, -17, der(17p), -18, and -21, were only rarely seen post-SCT. Comparing the cytogenetic features in relation to type of SCT revealed that balanced aberrations were significantly more common after allo than after auto SCT (64 and 22%, respectively, P=0.03). In addition, there was a trend as regards hyperdiploidy being more common after auto (P=0.07) and pseudodiploidy being more frequent after allo SCT (P=0.09). Possible reasons for these differences are discussed.

Adolescent↗
PubMed2006

Identification of cryptic aberrations and characterization of translocation breakpoints using array CGH in high hyperdiploid childhood acute lymphoblastic leukemia.

High hyperdiploidy, characterized by non-random trisomies, is the largest cytogenetic subgroup in childhood acute lymphoblastic leukemia (ALL). It is not known whether the gained chromosomes are sufficient for leukemogenesis or if additional genetic aberrations are necessary. However, the suboptimal chromosome morphology of hyperdiploid ALLs makes detection of structural abnormalities difficult if using cytogenetic techniques; alternative methods are, therefore, needed. We performed array comparative genome hybridization (CGH) analyses, with a resolution of 100 kb, of eight cases of high hyperdiploid childhood ALL to characterize structural abnormalities found with G-banding/multicolor fluorescence in situ hybridization (FISH) and to detect novel changes. The non-centromeric breakpoints of four rearrangements, including three translocations and one 1q duplication, were narrowed down to <0.2 Mb. Furthermore, four submicroscopic imbalances involving 0.6-2.7 Mb were detected, comprising two segmental duplications involving 1q22 and 12q24.31 in one case and two hemizygous deletions in 12p13.2-31 - including ETV6 - and in 13q32.3-33.1 in another case. Notably, FISH analysis of the latter revealed an associated reciprocal t(3;13)(q?;32.2-33.1). In conclusion, the array CGH analyses revealed putative leukemia-associated submicroscopic imbalances and rearrangements in 2/8 (25%) hyperdiploid ALLs. The detection and characterization of these additional genetic aberrations will most likely increase our understanding of the pathogenesis of high hyperdiploid childhood ALL.

Adolescent↗
PubMed2006

Molecular characterization of early-stage bladder carcinomas by expression profiles, FGFR3 mutation status, and loss of 9q.

We used gene expression profiling, mutation analyses of FGFR3 and TP53, and LOH analyses of chromosome 9 and the TP53 region on chromosome arm 17p, to molecularly characterize 75 Ta and T1 bladder carcinomas. We identified four major cellular processes related to cell cycle, protein synthesis, immune response, and extra cellular components that contribute to the expressional heterogeneity of early-stage urothelial cell carcinoma (UCC). Activating FGFR3 mutations were found at the highest frequency in G1 tumors (80%), and showed a strong correlation with FGFR3 expression. In contrast, G3 tumors displayed mutations in less than 10% of the cases and a low level of FGFR3 expression. Even though LOH on chromosome 9 was not associated with any specific expression pattern, our data indicate that loss of chromosome 9 is associated with tumor development rather than initiation. The combined analyses suggest the existence of two types of UCC tumors, one which is characterized by FGFR3 mutation or expression, high expression of protein synthesis genes, and low expression of cell cycle genes. Furthermore, the presented data underscore FGFR3 receptor involvement in urothelial cell transformation as the presence of FGFR3 mutations has a major impact on the global gene expression profile of bladder carcinomas.

Chromosomes, Human, Pair 17↗
PubMed2006

High-resolution genome-wide array-based comparative genome hybridization reveals cryptic chromosome changes in AML and MDS cases with trisomy 8 as the sole cytogenetic aberration.

Although trisomy 8 as the sole chromosome aberration is the most common numerical abnormality in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), little is known about its pathogenetic effects. Considering that +8 is a frequent secondary change in AML/MDS, cryptic--possibly primary--genetic aberrations may occur in cases with trisomy 8 as the apparently single anomaly. However, no such hidden anomalies have been reported. We performed a high-resolution genome-wide array-based comparative genome hybridization (array CGH) analysis of 10 AML/MDS cases with isolated +8, utilizing a 32K bacterial artificial chromosome array set, providing >98% coverage of the genome with a resolution of 100 kb. Array CGH revealed intrachromosomal imbalances, not corresponding to known genomic copy number polymorphisms, in 4/10 cases, comprising nine duplications and hemizygous deletions ranging in size from 0.5 to 2.2 Mb. A 1.8 Mb deletion at 7p14.1, which had occurred prior to the +8, was identified in MDS transforming to AML. Furthermore, a deletion including ETV6 was present in one case. The remaining seven imbalances involved more than 40 genes. The present results show that cryptic genetic abnormalities are frequent in trisomy 8-positive AML/MDS cases and that +8 as the sole cytogenetic aberration is not always the primary genetic event.

Acute Disease↗
PubMed2005

Gene expression profiling of leukemic cell lines reveals conserved molecular signatures among subtypes with specific genetic aberrations.

Hematologic malignancies are characterized by fusion genes of biological/clinical importance. Immortalized cell lines with such aberrations are today widely used to model different aspects of leukemogenesis. Using cDNA microarrays, we determined the gene expression profiles of 40 cell lines as well as of primary leukemias harboring 11q23/MLL rearrangements, t(1;19)[TCF3/PBX1], t(12;21)[ETV6/RUNX1], t(8;21)[RUNX1/CBFA2T1], t(8;14)[IGH@/MYC], t(8;14)[TRA@/MYC], t(9;22)[BCR/ABL1], t(10;11)[PICALM/MLLT10], t(15;17)[PML/RARA], or inv(16)[CBFB/MYH11]. Unsupervised classification revealed that hematopoietic cell lines of diverse origin, but with the same primary genetic changes, segregated together, suggesting that pathogenetically important regulatory networks remain conserved despite numerous passages. Moreover, primary leukemias cosegregated with cell lines carrying identical genetic rearrangements, further supporting that critical regulatory pathways remain intact in hematopoietic cell lines. Transcriptional signatures correlating with clinical subtypes/primary genetic changes were identified and annotated based on their biological/molecular properties and chromosomal localization. Furthermore, the expression profile of tyrosine kinase-encoding genes was investigated, identifying several differentially expressed members, segregating with primary genetic changes, which may be targeted with tyrosine kinase inhibitors. The identified conserved signatures are likely to reflect regulatory networks of importance for the transforming abilities of the primary genetic changes and offer important pathogenetic insights as well as a number of targets for future rational drug design.

Acute Disease↗
PubMed2004

Establishment and phenotypic characterization of human U937 cells with inducible P210 BCR/ABL expression reveals upregulation of CEACAM1 (CD66a).

Chronic myeloid leukemia (CML) is characterized by the expression of the P210 BCR/ABL fusion protein. The molecular mechanisms behind this oncogene-mediated hematological disease are, however, not fully understood. Here, we describe the establishment and phenotypic characterization of U937 cells in which P210 BCR/ABL can be conditionally expressed using tetracycline. The induction of BCR/ABL in the obtained clones resulted in a rapid phosphorylation of the STAT1, STAT3 and STAT5 molecules, consistent with the findings in other model systems. Phenotypic characterization of the clones revealed that BCR/ABL induces a slight decrease in the proliferation and viability, without a marked effect on cell cycle distribution, the rate of apoptosis or on cellular differentiation, as judged by several cell surface markers and capacity to reduce nitro blue tetrazolium. Interestingly, BCR/ABL was found to upregulate the expression of carcinoembryonic-related antigen (CEA)CAM1 (CD66a), which is a plasma membrane-linked glycoprotein belonging to the CEAs and involved in signal transduction and cellular adhesion. The expression of CEACAM1 was reversible upon imatinib treatment in BCR/ABL-expressing U937 cells as well as in BCR/ABL-positive K562 cells. The established cell lines may prove useful in further modeling and dissection of BCR/ABL-induced leukemogenesis.

Antigens, CD↗
PubMed2002

Prognostic implications of BCL6 rearrangement in uniformly treated patients with diffuse large B-cell lymphoma--a Nordic Lymphoma Group study.

The purpose of this study was to investigate the prognostic implications of BCL6 rearrangement in a uniformly treated population of patients with diffuse large B-cell lymphoma (DLBCL) and to characterise the relationship between BCL6 rearrangement and prognostic factors. A total of 269 patients with DLBCL entered a randomised trial comparing the chemotherapy regimen CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) to the MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin) regimen. In 44 cases, frozen tissue was available for assessment of BCL6 status by Southern blot analysis. BCL6 was rearranged in six of 43 evaluable cases (14%), and was associated with elevated lactate dehydrogenase (LDH), and a higher patient age. No association between BCL6 status and expression of BCL2, Ki-67 or TP53 was found. Patients presenting with BCL6 rearrangement displayed a weak trend towards better overall and failure-free survival (67 and 67% at 5 years), compared to patients with germline BCL6 (63 and 52%), but the difference was not statistically significant. In accordance with previously published series, the presence of BCL6 rearrangement does not define a prognostically distinct subgroup of DLBCL. Assessment of BCL6 status may, however, be of clinical interest when related to other prognostic variables.

Adolescent↗
PubMed2001

The incidence of trisomy 8 as a sole chromosomal aberration in myeloid malignancies varies in relation to gender, age, prior iatrogenic genotoxic exposure, and morphology.

Although trisomy 8 as a sole change is one of the most common chromosomal abnormalities in myeloid malignancies, it is largely unknown if the incidence of this aberration is influenced by other factors of clinical importance. In the present study, the frequencies of isolated +8 in relation to gender, age, previous treatment with chemo- or radiotherapy, and morphologic subtype were ascertained in published, as well as in our own unpublished, cases of acute myeloid leukemia (AML; n=4,246), myelodysplastic syndromes (MDS; n=1,817), and chronic myeloproliferative disorders (MPD; n=530). The frequencies of +8 were higher in MDS and MPD than in AML (7.5% vs. 5.6%; P<0.01) and varied among the morphologic subtypes of AML and MDS (P<0.001 and P<0.05, respectively). Trisomy 8 was more common in women than in men with MPD (11% vs. 5.1%; P<0.05). Furthermore, the frequencies of +8 were higher in de novo AML and MDS than in treatment-related cases (6.0% vs. 2.8%; P<0.01 and 8.6% vs. 1.5%; P<0.001, respectively). The incidence also varied significantly with age in AML (P<0.001), being more common in elderly patients. Although the causes for this frequency heterogeneity remain to be elucidated, possible explanations may include different environmental exposures affecting the origin of +8 in AML, MDS, and MPD and the presence of different underlying cryptic primary aberrations.

Age Factors↗
PubMed2001

Fusion of the MORF and CBP genes in acute myeloid leukemia with the t(10;16)(q22;p13).

The CBP gene at 16p13 fuses to MOZ and MLL as a result of the t(8;16)(p11;p13) in acute (myelo)monocytic leukemias (AML M4/M5) and the t(11;16)(q23;p13) in treatment-related AML, respectively. We show here that a novel t(10;16)(q22;p13) in a childhood AML M5a leads to a MORF-CBP chimera. RT-PCR using MORF forward and CBP reverse primers amplified a MORF-CBP fusion in which nucleotide 3103 of MORF was fused in-frame with nucleotide 284 of CBP. Nested RT-PCR with CBP forward and MORF reverse primers generated a CBP-MORF transcript in which nucleotide 283 of CBP was fused in-frame with nucleotide 3104 of MORF. Genomic analyses revealed that the breaks were close to Alu elements in intron 16 of MORF and intron 2 of CBP and that duplications had occurred near the breakpoints. A database search using MORF cDNA enabled us to construct an exon-intron map of the MORF gene. The MORF-CBP protein retains the zinc fingers, two nuclear localization signals, the histone acetyltransferase (HAT) domain, a portion of the acidic domain of MORF and the CBP protein downstream of codon 29. Thus, the part of CBP encoding the RARA-binding domain, the CREB-binding domain, the three Cys/His-rich regions, the bromodomain, the HAT domain and the Glu-rich domains is present. In the reciprocal CBP-MORF, part of the acidic domain and the C-terminal Ser- and Met-rich regions of MORF are likely to be driven by the CBP promoter. Since both fusion transcripts were present, their exact role in the leukemogenic process remains to be elucidated.

Acetyltransferases↗
PubMed2001

Isodicentric 7p, idic(7)(q11.2), in acute myeloid leukemia associated with older age and favorable response to induction chemotherapy: a new clinical entity?

Three adult de novo acute myeloid leukemias (AML M1, M2, and M4) with an isochromosome 7p are presented. No additional abnormalities were detected by G-band and multicolor, using combined binary ratio labeling, fluorescence in situ hybridization (FISH) analyses, indicating that the i(7p) was the sole, i.e., the primary, chromosomal aberration. Although the patients were elderly--68, 72, and 78 years old--they all responded very well to chemotherapy, achieving complete remission lasting more than a year. Further FISH analyses, using painting, centromeric, as well as 7q11.2-specific YAC probes, revealed that the i(7p) contained two centromeres and that the breakpoints were located in 7q11.2. Thus, the abnormality should formally be designated idic(7)(q11.2). The detailed mapping disclosed a breakpoint heterogeneity, with the breaks in 7q11.2 varying among the cases, being at least 1,310 kb apart. Furthermore, the breakpoints also differed within one of the cases, being located on both the proximal and the distal side of the most centromeric probe used. Based on our three patients, as well as on a previously reported 82-year-old patient with AML M2 and idic(7)(q11) as the only chromosomal change, we suggest that this abnormality, as the sole anomaly, is associated with AML in elderly patients who display a good response to induction chemotherapy and, hence, have a favorable prognosis. Furthermore, the heterogeneous breakpoints in 7q11.2 suggest that the important functional outcome of the idic(7)(q11.2) is the genomic imbalance incurred, i.e., gain of 7p and loss of 7q material, rather than a rearrangement of a specific gene.

Aged↗
PubMed2001

Fusion of the BCR and the fibroblast growth factor receptor-1 (FGFR1) genes as a result of t(8;22)(p11;q11) in a myeloproliferative disorder: the first fusion gene involving BCR but not ABL.

Constitutive activation of tyrosine kinases as a consequence of chromosomal translocations, forming fusion genes, plays an important role in the development of hematologic malignancies, in particular, myeloproliferative syndromes (MPSs). In this respect, the t(9;22)(q34;q11) that results in the BCR/ABL fusion gene in chronic myeloid leukemia is one of the best-studied examples. The fibroblast growth factor receptor 1 (FGFR1) gene at 8p11 encodes a transmembrane receptor tyrosine kinase and is similarly activated by chromosomal translocations, in which three alternative genes-ZNF198 at 13q12, CEP110 at 9q34, and FOP at 6q27-become fused to the tyrosine kinase domain of FGFR1. These 8p11-translocations are associated with characteristic morphologic and clinical features, referred to as "8p11 MPS." In this study, we report the isolation and characterization of a novel fusion gene in a hematologic malignancy with a t(8;22)(p11;q11) and features suggestive of 8p11 MPS. We show that the breakpoints in the t(8;22) occur within introns 4 and 8 of the BCR and FGFR1 genes, respectively. On the mRNA level, the t(8;22) results in the fusion of BCR exons 1-4 in-frame with the tyrosine kinase domain of FGFR1 as well as in the expression of a reciprocal FGFR1/BCR chimeric transcript. By analogy with data obtained from previously characterized fusion genes involving FGFR1 and BCR/ABL, it is likely that the oligomerization domain contributed by BCR is critical and that its dimerizing properties lead to aberrant FGFR1 signaling and neoplastic transformation.

Aged↗
PubMed2001

Paired multiplex reverse-transcriptase polymerase chain reaction (PMRT-PCR) analysis as a rapid and accurate diagnostic tool for the detection of MLL fusion genes in hematologic malignancies.

The MLL gene in chromosome band 11q23 is frequently rearranged in acute lymphoblastic and acute myeloid leukemias. To date, more than 50 different chromosomal regions are known to participate in translocations involving 11q23, many of which affect MLL. The pathogenetically important outcome of these rearrangements is most likely the creation of a fusion gene consisting of the 5' part of the MLL gene and the 3' end of the partner gene. Although abnormalities of the MLL gene as such are generally associated with poor survival, recent data suggest that the prognostic impact varies among the different fusion genes generated. Hence, detection of the specific chimeric gene produced is important for proper prognostication and clinical decision making. We have developed a paired multiplex reverse-transcriptase polymerase chain reaction analysis to facilitate a rapid and accurate detection of the most frequent MLL fusion genes in adult and childhood acute leukemias. To increase the specificity, two sets of primers were designed for each fusion gene, and these paired primer sets were run in parallel in two separate multiplex one-step PCR reactions. Using the described protocol, we were able to amplify successfully, in one single assay, the six clinically relevant fusion genes generated by the t(4;11)(q21;q23) [MLL/AF4], t(6;11)(q27;q23) [MLL/AF6], t(9;11)(p21-22;q23) [MLL/AF9], t(10;11)(p11-13;q23) [MLL/AF10], t(11;19)(q23;p13.1) [MLL/ELL], and t(11;19)(q23; p13.3) [MLL/ENL] in cell lines, as well as in patient material.

Biomarkers, Tumor↗
PubMed2000

RT-PCR analysis of the MOZ-CBP and CBP-MOZ chimeric transcripts in acute myeloid leukemias with t(8;16)(p11;p13).

The translocation t(8;16)(p11;p13) is associated with a subtype of acute monocytic leukemia (AML M5) characterized morphologically by erythrophagocytosis and clinically by a poor prognosis. The t(8;16) fuses the MOZ gene from 8p11 with the CBP (also named CREBBP) gene from 16p13. Previously published studies of MOZ and CBP rearrangements in t(8;16)-positive AML have used fluorescence in situ hybridization and Southern blot methodologies, whereas attempts to amplify and to analyze further the chimeric MOZ-CBP and CBP-MOZ transcripts by means of reverse transcriptase-polymerase chain reaction (RT-PCR) have largely been unsuccessful. In the only t(8;16) that has been described at the sequence level using RT-PCR, the CBP-MOZ fusion was found to be out-of-frame, suggesting that the reciprocal MOZ-CBP transcript is the essential one for leukemogenesis. We have developed an RT-PCR strategy that enables us to detect the MOZ-CBP as well as the CBP-MOZ fusions in the two AML M5 with t(8;16)(p11;p13) analyzed. In both leukemias, the combination of a MOZ forward and a CBP reverse primer amplified a strongly expressed 1,128 bp fragment (type I transcript) and a weakly expressed 415 bp fragment (type II transcript). In the type I transcript, nucleotide (nt) 3,745 of MOZ was fused in-frame with nt 284 of CBP, whereas in the type II transcript, nt 3,745 of MOZ was fused out-of-frame with nt 997 of CBP. Nested PCR with a combination of two forward CBP and two reverse MOZ primers amplified CBP-MOZ chimeric transcripts in both cases. Direct sequence analysis showed that nt 283 of CBP was fused in-frame with nt 3,746 of MOZ, that the initiation ATG codon of the CBP gene remained intact, and that there was no mutation or deletion in the part of the CBP gene included in the CBP-MOZ transcript. Thus, the data we present are not informative with regard to the question whether it is the MOZ-CBP or the CBP-MOZ transcript that is leukemogenic. The present RT-PCR method may be of value for rapid identification of the t(8;16) and also for further molecular genetic studies of the two fusion transcripts and their roles in leukemogenesis.

Acetyltransferases↗
PubMed2000

Granulocytic sarcomas in body cavities in childhood acute myeloid leukemias with 11q23/MLL rearrangements.

Three childhood acute monoblastic leukemias (AML M5) with granulocytic sarcomas (GSs) are described. All displayed 11q23/MLL abnormalities, t(9;11)(p22;q23) in two cases and t(11;17)(q23;q21) in one case, constituting around 20% of all 11q23-positive AML cytogenetically investigated in our department. Two of the patients had GS in multiple locations, and all three had abdominal GS. In two of them, t(9;11)-positive GS was diagnosed prior to the diagnosis of AML. Fourteen (1.9%) of 752 published AML cases with 11q23 aberrations have had GS, either as a presenting feature or during disease progression. The incidence of GS has varied significantly (P < 0.05) between children (3.8%) and adults (0.8%). The most common AML subtype has been AML M5 ( approximately 75%) and the most frequent GS sites have been the skin, abdomen, orbit, and thorax. Considering the possibility of underreporting of GS in published cases and the relatively high frequency in our own series, we believe that 11q23/MLL rearrangements may predispose to GS development. Although extramedullary infiltrates in the skin are known to be frequent in cases of AML M5, which is often associated with 11q23 aberrations, the present findings indicate that GS in the abdomen, orbit, and thorax may also be common, especially in pediatric AML. Thus, the possibility of 11q23/MLL-positive GS should be suspected when tumors of uncertain derivation occur in these sites. Finally, the identification of 11q23/MLL abnormalities in GSs in two patients without overt AML underscores the importance of using cytogenetic and molecular genetic investigations as a diagnostic approach in the evaluation of tumorous lesions of unknown origin. Genes Chromosomes Cancer 27:136-142, 2000.

Abdomen↗
PubMed1999

Isochromosome 17q in blast crisis of chronic myeloid leukemia and in other hematologic malignancies is the result of clustered breakpoints in 17p11 and is not associated with coding TP53 mutations.

An isochromosome of the long arm of chromosome 17, i(17q), is the most frequent genetic abnormality observed during the disease progression of Philadelphia chromosome-positive chronic myeloid leukemia (CML), and has been described as the sole anomaly in various other hematologic malignancies. The i(17q) hence plays a presumably important pathogenetic role both in leukemia development and progression. This notwithstanding, the molecular consequences of this abnormality have not been investigated in detail. We have analyzed 21 hematologic malignancies (8 CML in blast crisis, 8 myelodysplastic syndromes [MDS], 2 acute myeloid leukemias, 2 chronic lymphocytic leukemias, and 1 acute lymphoblastic leukemia) with i(17q) by fluorescence in situ hybridization (FISH). Using a yeast artificial chromosome (YAC) contig, derived from the short arm of chromosome 17, all cases were shown to have a breakpoint in 17p. In 12 cases, the breaks occurred within the Smith-Magenis Syndrome (SMS) common deletion region in 17p11, a gene-rich region which is genetically unstable. In 10 of these 12 cases, we were able to further map the breakpoints to specific markers localized within a single YAC clone. Six other cases showed breakpoints located proximally to the SMS common deletion region, but still within 17p11, and yet another case had a breakpoint distal to this region. Furthermore, using chromosome 17 centromere-specific probes, it could be shown that the majority of the i(17q) chromosomes (11 of 15 investigated cases) were dicentric, ie, they contained two centromeres, strongly suggesting that i(17q) is formed through an intrachromosomal recombination event, and also implicating that the i(17q), in a formal sense, should be designated idic(17)(p11). Because i(17q) formation results in loss of 17p material, potentially uncovering the effect of a tumor suppressor on the remaining 17p, the occurrence of TP53 mutations was studied in 17 cases by sequencing the entire coding region. In 16 cases, no TP53 mutations were found, whereas one MDS displayed a homozygous deletion of TP53. Thus, our data suggest that there is no association between i(17q) and coding TP53 mutations, and that another tumor suppressor gene(s), located in proximity of the SMS common deletion region, or in a more distal location, is of pathogenetic importance in i(17q)-associated leukemia.

Adolescent↗
PubMed1999

Cytogenetic polyclonality in hematologic malignancies.

The present study was undertaken to ascertain the frequency of cytogenetic polyclonality in various hematologic malignancies and to investigate whether morphologic subgroup, age, gender, or previous genotoxic exposure influences the incidence. Among 2,243 cytogenetically investigated hematologic malignancies, 10 acute myeloid leukemias (AML), 5 myelodysplastic syndromes (MDS), 2 acute lymphoblastic leukemias (ALL), 1 acute undifferentiated leukemia (AUL), 1 atypical Philadelphia chromosome-negative (Ph-) chronic myeloid leukemia (CML), 1 chronic myeloproliferative disorder (CMD), and 1 chronic lymphoproliferative disorder (CLD) with karyotypically unrelated clones were identified, constituting 2.6% of AML, 1.6% of MDS, 0.8% of ALL, 13% of AUL, 9.1% of Ph- CML, 1.5% of CMD, and 2.8% of CLD with chromosomal abnormalities. In contrast to the cytogenetic features, the X-inactivation pattern was monoclonal in the two informative female patients that could be investigated. Among 17,733 karyotypically aberrant published cases surveyed, significant frequency differences (P < 0.001) were discerned: 1.7% of 6,526 AML, 3.4% of 2,391 MDS, 0.4% of 1,920 Ph+ CML, 2.9% of 856 CMD, 0.9% of 4,226 ALL, and 5.8% of 1,814 CLD displayed unrelated clones. The incidence of cytogenetic polyclonality did not differ significantly among the MDS, CMD, or ALL subgroups, between males and females, between children (< 16 years) and adults, or between B- and T-cell ALL, whereas the frequencies varied among the AML FAB types (P < 0.05), among the different CLD entities (P < 0.001), and between B- and T-cell CLD (P < 0.001). Furthermore, the incidence was higher in therapy-related AML and MDS than in de novo AML and MDS (P < 0.001 and P < 0.01, respectively).

Adolescent↗