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.

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.

scholarly journals Juvenile Myelomonocytic Leukemia (JMML): A Mimicker of KMT2A-Rearranged Acute Myeloid Leukemia (AML)

2020 ◽  
Author(s):  
Ashraf Abdullah Saad
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Hematologic Malignancies ◽  
Driver Mutations ◽  
Juvenile Myelomonocytic Leukemia ◽  
Monosomy 7 ◽  
Acute Myelomonocytic Leukemia ◽  
Myelomonocytic Leukemia ◽  
Acute Myeloid

Juvenile myelomonocytic leukemia (JMML) is the most confusing mimicker of KMT2A-rearranged acute myeloid leukemia (AML). Clinical presentation, age of susceptibility (infancy or early childhood) and abnormal monocytosis are common clinical features. To complicate matters, JMML morphologically resemble acute myelomonocytic leukemia (AML M4) and distinction must be made based on accurate blast and promonocyte counts. As treatment significantly varies, AML/JMML overlap can lead to catastrophic consequences that can be avoided by timely management. Therefore, meticulous knowledge of JMML is essential to treat patients with hematologic malignancies. The pathognomic feature of JMML is increased infiltration of the peripheral blood, bone marrow, and viscera by abnormal myelomonocytic cells. Molecular diagnostics has generated substantial dividends in dissecting the genetic basis of JMML. We can now molecularly confirm the diagnosis of JMML in approximately over 90% of patients who harbor driver mutations in KRAS, NRAS, PTPN11, NF1, or CBL genes. The presence of monosomy 7 is a classic feature of JMML that can support the diagnosis in many cases. On the other hand, cytogenetics and Fluorescence in situ hybridization analysis (FISH) are indispensable to differentiate KMT2A-rearranged AML from JMML. In particular, AML with t(9;11) is associated with monocytic features that can be easily mistaken for JMML.

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.

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 De novo adult acute myeloid leukemia with two new mutations in juxtatransmembrane domain of the FLT3 gene: a case report

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Ismael F. Alarbeed ◽  
Abdulsamad Wafa ◽  
Faten Moassass ◽  
Bassel Al-Halabi ◽  
Walid Al-Achkar ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Chromosomal Abnormalities ◽  
Molecular Genetic ◽  
Type A ◽  
Chemotherapeutic Treatment ◽  
Acute Myeloid ◽  
New Mutations

Abstract Background Approximately 30% of adult acute myeloid leukemia (AML) acquire within fms-like tyrosine kinase 3 gene (FLT3) internal tandem duplications (FLT3/ITDs) in their juxtamembrane domain (JMD). FLT3/ITDs range in size from three to hundreds of nucleotides, and confer an adverse prognosis. Studies on a possible relationship between of FLT3/ITDs length and clinical outcomes in those AML patients were inconclusive, yet. Case presentation Here we report a 54-year-old Arab male diagnosed with AML who had two FLT3-ITD mutations in addition to NPM1 mutation. Cytogenetic approaches (banding cytogenetics) and fluorescence in situ hybridization (FISH) using specific probes to detect translocations t(8;21), t(15;17), t(16;16), t(12;21), and deletion del(13q)) were applied to exclude chromosomal abnormalities. Molecular genetic approaches (polymerase chain reaction (PCR) and the Sanger sequencing) identified a yet unreported combination of two new mutations in FLT3-ITDs. The first mutation induced a frameshift in JMD, and the second led to a homozygous substitution of c.1836T>A (p.F612L) also in JMD. Additionally a NPM1 type A mutation was detected. The first chemotherapeutic treatment was successful, but 1 month after the initial diagnosis, the patient experienced a relapse and unfortunately died. Conclusions To the best of our knowledge, a combination of two FLT3-ITD mutations in JMD together with an NPM1 type A mutation were not previously reported in adult AML. Further studies are necessary to prove or rule out whether the size of these FLT3-ITDs mutations and potential other double mutations in FLT3-ITD are correlated with the observed adverse outcome.

scholarly journals DNA damage in acute myeloid leukemia patients of Northern Mexico

2017 ◽  
Author(s):  
Martha I. Dávila-Rodríguez ◽  
Elva I. Cortés-Gutiérrez ◽  
Roberto Hernández-Valdés ◽  
Karla Guzmán-Cortés ◽  
Rosa E. De León-Cantú ◽  
...  
Keyword(s):  
Dna Damage ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Fluorescent In Situ Hybridization ◽  
Control Group ◽  
Repair Pathway ◽  
Blood Leukocytes ◽  
Northern Mexico ◽  
Acute Myeloid

The purpose of this study was to evaluate DNA damage in the whole genome of peripheral blood leukocytes from patients with acute myeloid leukemia (AML) compared with a control group using DNA breakage detection-fluorescent in situ hybridization (DBD-FISH). Our results suggest that the DNA damage detected in patients with newly diagnosed AML was similar to that observed for the controls; this might be explained by the stimulation of a repair pathway by the pathogenesis itself. These findings indicate that inhibiting the repair pathway could be proposed to enhance the efficacy of chemotherapy.

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