scholarly journals 17p Deletion in Acute Myeloid Leukemia and Myelodysplastic Syndrome. Analysis of Breakpoints and Deleted Segments by Fluorescence In Situ

Blood ◽  
1998 ◽  
Vol 91 (3) ◽  
pp. 1008-1015 ◽  
Author(s):  
Valérie Soenen ◽  
Claude Preudhomme ◽  
Christophe Roumier ◽  
Agnès Daudignon ◽  
Jean Luc Laı̈ ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Myeloid Leukemia ◽  
P53 Gene ◽  
P53 Mutation ◽  
Chromosome 17 ◽  
Gene Probe ◽  
Fish Analysis ◽  
Acute Myeloid

Recently, we and other groups reported in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) a strong correlation between cytogenetic rearrangements leading to 17p deletion, a typical form of dysgranulopoiesis combining pseudo-Pelger-Huët hypolobulation and small vacuoles in neutrophils, and p53 mutation. To gain further insight into this “17p-syndrome,” we studied 17 cases of AML and MDS with 17p deletion by whole chromosome painting (WCP) and fluorescence in situ hybridization (FISH) with probes spanning the 17p arm, including a p53 gene probe. Cytogenetically, 15 patients had unbalanced translocation between chromosome 17 and another chromosome (chromosome 5 in nine cases and unidentified chromosome -add 17p- in three cases), one patient had monosomy 17, and one had i(17q). All rearrangements appeared to result in 17p deletion. Sixteen patients had additional cytogenetic rearrangements. WCP analysis confirmed the cytogenetic interpretation in all cases and identified one of the cases of add 17p as a t(17;22). WCP also identified chromosome 17 material on a marker or ring chromosome in two cases of t(5;17). FISH analysis with 17p markers made in 16 cases showed no deletion of the 17p markers studied in the last two patients, who had no typical dysgranulopoiesis; p53 mutation analysis in one of them was negative. In the 14 other cases, FISH showed a 17p deletion of variable extent but that always included deletion of the p53 gene. All 14 patients had typical dysgranulopoiesis, and all but one had p53 mutation and/or overexpression. These findings reinforce the morphologic, cytogenetic, and molecular correlation found in the 17p- syndrome and suggest a pathogenetic role for inactivation of tumor suppressor gene(s) located in 17p, especially the p53 gene.

scholarly journals 17p Deletion in Acute Myeloid Leukemia and Myelodysplastic Syndrome. Analysis of Breakpoints and Deleted Segments by Fluorescence In Situ

Blood ◽  
1998 ◽  
Vol 91 (3) ◽  
pp. 1008-1015 ◽  
Author(s):  
Valérie Soenen ◽  
Claude Preudhomme ◽  
Christophe Roumier ◽  
Agnès Daudignon ◽  
Jean Luc Laı̈ ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Myeloid Leukemia ◽  
P53 Gene ◽  
P53 Mutation ◽  
Chromosome 17 ◽  
Gene Probe ◽  
Fish Analysis ◽  
Acute Myeloid

Abstract Recently, we and other groups reported in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) a strong correlation between cytogenetic rearrangements leading to 17p deletion, a typical form of dysgranulopoiesis combining pseudo-Pelger-Huët hypolobulation and small vacuoles in neutrophils, and p53 mutation. To gain further insight into this “17p-syndrome,” we studied 17 cases of AML and MDS with 17p deletion by whole chromosome painting (WCP) and fluorescence in situ hybridization (FISH) with probes spanning the 17p arm, including a p53 gene probe. Cytogenetically, 15 patients had unbalanced translocation between chromosome 17 and another chromosome (chromosome 5 in nine cases and unidentified chromosome -add 17p- in three cases), one patient had monosomy 17, and one had i(17q). All rearrangements appeared to result in 17p deletion. Sixteen patients had additional cytogenetic rearrangements. WCP analysis confirmed the cytogenetic interpretation in all cases and identified one of the cases of add 17p as a t(17;22). WCP also identified chromosome 17 material on a marker or ring chromosome in two cases of t(5;17). FISH analysis with 17p markers made in 16 cases showed no deletion of the 17p markers studied in the last two patients, who had no typical dysgranulopoiesis; p53 mutation analysis in one of them was negative. In the 14 other cases, FISH showed a 17p deletion of variable extent but that always included deletion of the p53 gene. All 14 patients had typical dysgranulopoiesis, and all but one had p53 mutation and/or overexpression. These findings reinforce the morphologic, cytogenetic, and molecular correlation found in the 17p- syndrome and suggest a pathogenetic role for inactivation of tumor suppressor gene(s) located in 17p, especially the p53 gene.

NUP98 is fused to the NSD3 gene in acute myeloid leukemia associated with t(8;11)(p11.2;p15)

Blood ◽  
2002 ◽  
Vol 99 (10) ◽  
pp. 3857-3860 ◽  
Author(s):  
Roberto Rosati ◽  
Roberta La Starza ◽  
Angelo Veronese ◽  
Ana Aventin ◽  
Christine Schwienbacher ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Hematologic Malignancies ◽  
Fish Analysis ◽  
Fusion Partner ◽  
First Time ◽  
Classical Cytogenetics ◽  
Split Signal ◽  
Acute Myeloid

Fusion between the NUP98 and NSD3genes in a patient with acute myeloid leukemia associated with t(8;11)(p11.2;p15), is reported for the first time. The t(8;11)(p11.2;p15) was identified by classical cytogenetics. Fluorescence in situ hybridization (FISH) analysis revealed a split signal with a mix of BAC 118H17 and 290A12, indicating the translocation disrupted NUP98. FISH restriction at 8p11-12 showed a split of BAC 350N15. Molecular investigations into candidate genes in this BAC showed the NUP98 fusion partner at 8p11.2 was the NSD3 gene. To date the NSD3 gene has never been implicated in hematologic malignancies.

Multiplex Fluorescence In Situ Hybridization (M-FISH) in the Detection of Complex Karyotypic Abnormalities of Acute Myeloid Leukemia and Myelodysplastic Syndromes.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4504-4504
Author(s):  
Jianyong Li ◽  
Jinlan Pan ◽  
Bing Xiao ◽  
Li Ma ◽  
Hairong Qiu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Myelodysplastic Syndromes ◽  
Myeloid Leukemia ◽  
Chromosome Analysis ◽  
Chromosome 17 ◽  
Structural Aberrations ◽  
Acute Myeloid

Abstract The complex chromosome abnormalities (CCAs) were one of the most important poor prognostic risk factors in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Chromosome analysis using classical cytogenetic banding techniques fails to completely resolve complex karyotypes and cryptic translocations. The technique of multiplex fluorescence in situ hybridization (M-FISH) allow for the simultaneous visualization of all chromosomes of a metaphase in a single hybridization step and thereby enable to comprehensively analyze complex karyotypes and the identification of new and cryptic translocations. To investigate the value of M-FISH in the detection of complex karyotypic abnormalities of AML and MDS. M-FISH was used in combination with interphase-FISH to study 24 cases of AML and MDS with CCAs showed by R-banding of conventional cytogenetics (CC). In 14 cases of AML with CCAs, 4 gains of whole chromosome and 4 losses of whole chromosome were confirmed by M-FISH, while 12 losses of whole chromosome were revised as derivative chromosomes resulted from various structural aberrations. 26 derivative chromosomes and 19 marker chromosomes were characterized precisely by M-FISH. Most of them were unbalanced translocations, including 2 complex t(8;21), which have not been previously described:t(8;21), der(8) t(8;21) (8pter→8q22::21q22→21qter), der(21) t(8;21;8) (8qter→ 8q22::21p13→ 21q22::8q22→ 8qter) and t(21;8;18;1), der(8) t(8;21) (8pter→ 8q22::21q22→ 21qter), der(21) t(21;8;18;1) (21p13→ 21q22::8q22→ 8q24::18?::1q?q?). In 10 cases of MDS, 37 kinds of structural rearrangements were detected by M-FISH including insertion, deletion, translocation and derivative chromosomes, and among them 34 kinds were unbalanced rearrangements, only 3 were balanced rearrangements including t(6;22)(q21;q12), t(9;19)(q13;p13) and t(3;5)( ?;?), 7 abnormalities were never reported before. The CCAs invloved nearly all chromosomes, of which the chromosome 17, 5 and 7 were invloved more frequent than the rest. Chromosomes 5, 17, 7 were involved in 15 cases (62.5%), 12 cases (50%) and 6 cases (25%) respecrively. We conclude that M-FISH could refine CCAs of AML and MDS patients, find or correct the missed or misidentified aberrations by CC analysis. Our findings confirm that M-FISH is a powerful tool to characterize complex karyotypes in AML and MDS.

scholarly journals Acute Myeloid Leukemia and Myelodysplastic Syndromes Following Essential Thrombocythemia Treated With Hydroxyurea: High Proportion of Cases With 17p Deletion

Blood ◽  
1998 ◽  
Vol 91 (2) ◽  
pp. 616-622 ◽  
Author(s):  
Yvon Sterkers ◽  
Claude Preudhomme ◽  
Jean-Luc Laı̈ ◽  
Jean-Loup Demory ◽  
Marie-Thérèse Caulier ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cytogenetic Analysis ◽  
Myeloid Leukemia ◽  
Alkylating Agents ◽  
Myeloproliferative Disorders ◽  
P53 Mutation ◽  
Chromosome 17 ◽  
Molecular Characteristics ◽  
Acute Myeloid

Treatment with alkylating agents or radiophosphorous (32P) has been shown to carry a certain leukemogenic risk in myeloproliferative disorders (MPDs), including essential thrombocytemia (ET). The leukemogenic risk associated to treatment with hydroxyurea in ET, on the other hand, is generally considered to be relatively low. Between 1970 and 1991, we diagnosed ET in 357 patients, who were monitored until 1996. One or several therapeutic agents had been admistered to 326 patients, including hydroxyurea (HU) in 251 (as only treatment in 201), pipobroman in 43, busulfan in 41, and32P in 40. With a median follow-up duration of 98 months, 17 patients (4.5%) had progressed to acute myeloid leukemia (AML; six cases) or myelodysplastic syndrome (MDS; 11 cases). Fourteen of these patients had received HU, as sole treatment in seven cases, and preceded or followed by other treatment in seven cases, mainly pipobroman (five cases). The remaining three leukemic progressions occurred in patients treated with 32P (two cases) and busulfan (one case). The incidence of AML and MDS after treatment, using 32P alone and 32P with other agents, busulfan alone and with other agents, HU alone and with others agents, and pipobroman alone and with other agents was 7% and 9%, 3% and 17%, 3.5% and 14%, and 0% and 16%, respectively. Thirteen of 17 patients who progressed to AML or MDS had successful cytogenetic analysis. Seven of them had rearrangements of chromosome 17 (unbalanced translocation, partial or complete deletion, isochromosome 17q) that resulted in 17p deletion. They also had a typical form of dysgranulopoiesis combining pseudo Pelger Hüet hypolobulation and vacuoles in neutrophils, and p53 mutation, as previously described in AML and MDS with 17p deletion. Those seven patients had all received HU, as the only therapeutic agent in three, and followed by pipobroman in three. The three patients who had received no HU and progressed to AML or MDS had no 17p deletion. A review of the literature found cytogenetic analysis in 35 cases of AML and MDS occurring after ET, 11 of whom had been treated with HU alone. Five of 35 patients had rearrangements that resulted in 17p deletion. Four of them had been treated with HU alone. These results show that treatment with HU alone is associated with a leukemic risk of approximately 3.5%. A high proportion of AML and MDS occurring in ET treated with HU (alone or possibly followed by pipobroman) have morphologic, cytogenetic, and molecular characteristics of the 17p− syndrome. These findings suggest that widespread and prolonged use of HU in ET may have to be reconsidered in some situations, such as asymptomatic ET.

scholarly journals Acute Myeloid Leukemia and Myelodysplastic Syndromes Following Essential Thrombocythemia Treated With Hydroxyurea: High Proportion of Cases With 17p Deletion

Blood ◽  
1998 ◽  
Vol 91 (2) ◽  
pp. 616-622 ◽  
Author(s):  
Yvon Sterkers ◽  
Claude Preudhomme ◽  
Jean-Luc Laı̈ ◽  
Jean-Loup Demory ◽  
Marie-Thérèse Caulier ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cytogenetic Analysis ◽  
Myeloid Leukemia ◽  
Alkylating Agents ◽  
Myeloproliferative Disorders ◽  
P53 Mutation ◽  
Chromosome 17 ◽  
Molecular Characteristics ◽  
Acute Myeloid

Abstract Treatment with alkylating agents or radiophosphorous (32P) has been shown to carry a certain leukemogenic risk in myeloproliferative disorders (MPDs), including essential thrombocytemia (ET). The leukemogenic risk associated to treatment with hydroxyurea in ET, on the other hand, is generally considered to be relatively low. Between 1970 and 1991, we diagnosed ET in 357 patients, who were monitored until 1996. One or several therapeutic agents had been admistered to 326 patients, including hydroxyurea (HU) in 251 (as only treatment in 201), pipobroman in 43, busulfan in 41, and32P in 40. With a median follow-up duration of 98 months, 17 patients (4.5%) had progressed to acute myeloid leukemia (AML; six cases) or myelodysplastic syndrome (MDS; 11 cases). Fourteen of these patients had received HU, as sole treatment in seven cases, and preceded or followed by other treatment in seven cases, mainly pipobroman (five cases). The remaining three leukemic progressions occurred in patients treated with 32P (two cases) and busulfan (one case). The incidence of AML and MDS after treatment, using 32P alone and 32P with other agents, busulfan alone and with other agents, HU alone and with others agents, and pipobroman alone and with other agents was 7% and 9%, 3% and 17%, 3.5% and 14%, and 0% and 16%, respectively. Thirteen of 17 patients who progressed to AML or MDS had successful cytogenetic analysis. Seven of them had rearrangements of chromosome 17 (unbalanced translocation, partial or complete deletion, isochromosome 17q) that resulted in 17p deletion. They also had a typical form of dysgranulopoiesis combining pseudo Pelger Hüet hypolobulation and vacuoles in neutrophils, and p53 mutation, as previously described in AML and MDS with 17p deletion. Those seven patients had all received HU, as the only therapeutic agent in three, and followed by pipobroman in three. The three patients who had received no HU and progressed to AML or MDS had no 17p deletion. A review of the literature found cytogenetic analysis in 35 cases of AML and MDS occurring after ET, 11 of whom had been treated with HU alone. Five of 35 patients had rearrangements that resulted in 17p deletion. Four of them had been treated with HU alone. These results show that treatment with HU alone is associated with a leukemic risk of approximately 3.5%. A high proportion of AML and MDS occurring in ET treated with HU (alone or possibly followed by pipobroman) have morphologic, cytogenetic, and molecular characteristics of the 17p− syndrome. These findings suggest that widespread and prolonged use of HU in ET may have to be reconsidered in some situations, such as asymptomatic ET.

Trisomy 22 as the Sole Abnormality Is an Important Marker for Inversion 16 in Acute Myeloid Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4445-4445
Author(s):  
Jianyong Li ◽  
Huifen Zhou ◽  
Lijuan Chen ◽  
Jinlan Pan ◽  
Hairong Qiu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Myeloid Leukemia ◽  
Fish Analysis ◽  
Trisomy 8 ◽  
Conventional Cytogenetics ◽  
Acute Myeloid ◽  
Important Marker

Abstract Inv(16) has been reported in 10%~12% of acute myeloid leukemia (AML), mostly being associated with the M4Eo subtype, and is associated with a relatively favorable outcome. However, it is a cryptic rearrangement and often difficult to recognize in conventional cytogenetics (CC). Trisomy 22 is an uncommon karyotypic aberration in AML and is often associated with inv(16)(p13q22). In order to explore the value of trisomy 22 in the diagnosis of AML with inv(16), dual-color interphase fluorescence in situ hybridization (FISH) was performed in 19 AML cases with trisomy 22 abnormality. The probe was two-color break apart probe for CBFb with SpectrumRed on the centromeric side and SpectrumGreen on the telomeric side. And the results were compared with that of R-banding CC. CC did not reveal inv(16) in any of the 19 AML with trisomy 22, but FISH analysis showed inv(16) in 11 cases and del(16)(q22) in one case. Among 11 cases with inv(16), 9 were trisomy 22 as the sole abnormality, one was complicated with trisomy 8, and one was del(16)(q22). Four AML patients with trisomy 22 and inv(16) were analyzed by multiplex FISH (M-FISH) which revealed trisomy 22 only. This study further confirmed that trisomy 22 as the sole abnormality can be regarded as an important marker for the inv(16) in AML.

Comparison of Fluorescence In Situ Hybridization for EGR1 Vs CSF1R for the Detection of Del(5q) in Myelodysplasia and Acute Myeloid Leukemia.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1641-1641
Author(s):  
Yang Sun ◽  
James R. Cook
Keyword(s):  
Acute Myeloid Leukemia ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Myeloid Leukemia ◽  
Refractory Anemia ◽  
Routine Practice ◽  
Fish Analysis ◽  
Normal Ranges ◽  
Acute Myeloid

Abstract The detection of del(5q) in myelodysplastic syndrome (MDS) provides useful information to guide the choice of therapy, given the efficacy of lenalidomide in cases containing this abnormality. Fluorescence in situ hybridization (FISH) analysis offers the opportunity to specifically detect chromosomal abnormalities much more rapidly than metaphase cytogenetics, which may have a turnaround time of several weeks. However, it is currently unclear which chromosomal loci are the most appropriate to examine for detection of del(5q) in routine practice. The breakpoints on chromosome 5q are heterogeneous and two commonly deleted regions (CDR) have been described. The first CDR occurs in acute myeloid leukemia (AML) and high grade MDS and encompasses a region at 5q31 including the EGR1 locus. A second CDR, occurring in at least some cases reported as 5q- syndrome, centers around 5q33 and includes the CSF1R locus. We therefore examined whether FISH studies for EGR1, CSF1R, or a combination of both probes would provide the greatest clinical utility for detection of del(5q). 51 cases of myeloid neoplasms with del(5q) by metaphase cytogenetics were analyzed, including 5q- syndrome (n=8), refractory anemia with excess blasts (RAEB, n=8), refractory cytopenia with multilineage dysplasia (RCMD, n=6), MDS unclassifiable (n=1), therapy related MDS (n=1), myelodysplastic/myeloproliferative overlap syndromes (MDS/MPD, n=6), and AML (n=21). FISH studies using EGR1/D5S23, D5S721 and CSF1R/D5S23, D5S721 probes (Abbot Molecular, Abbot Park, IL) were performed on archival bone marrows (45 coverslip aspirate smears, 4 cytogenetic culture cell pellets, and 2 formalin fixed paraffin embedded clot sections). Normal ranges were established for each probe by analysis of appropriate negative control samples. Deletion of the EGR1 locus was detected in 49/51 (96%) cases, including each case of 5q- syndrome. The CSF1R locus, which could be analyzed in 48 cases, was deleted in 44 cases (92%). In cases with concordant results, a similar percentage of abnormal nuclei was identified with each probe. Two cases (1 MDS/MPD and 1 AML) displayed deletion of the EGR1 locus but a normal pattern for CSF1R. Two cases (1 AML and 1 MDS/MPD) showed no evidence of EGR1 or CSF1R deletion despite a del(5q) identified by metaphase cytogenetics. In conclusion, FISH for EGR1 is sufficient to successfully detect del(5q) in the vast majority of cases of MDS and AML containing this abnormality, including at least most cases of 5q- syndrome. Additional FISH studies for the CSF1R locus did not increase the diagnostic yield. Further studies will be required to determine if deletions of 5q involving EGR1 but not CSF1R influence the response to lenalidomide. A small number of cases of del(5q) are detected only by metaphase cytogenetics, possibly due to a small number of abnormal cells present prior to in vitro culture.

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