scholarly journals t(4;12)(q12;p13) ETV6-rearranged AML without eosinophilia does not involve PDGFRA: relevance for imatinib insensitivity

2021 ◽  
Author(s):  
Sarah Beth Mueller ◽  
Paola Dal Cin ◽  
Long Phi Le ◽  
Dora Dias-Santagata ◽  
Jochen K Lennerz ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Myeloid Leukemia ◽  
Clinical Course ◽  
Fish Analysis ◽  
Hematopoietic Malignancies ◽  
Archival Material ◽  
Eosinophilic Disorders ◽  
Aggressive Clinical Course ◽  
Genomic Regions

Acute myeloid leukemia (AML) with t(4;12)(q12;p13) translocation is rare, and often associated with an aggressive clinical course and poor prognosis. Previous reports based on fluorescence in-situ hybridization (FISH) analysis have suggested that ETV6-PDGFRA fusions are present in these patients despite the absence of eosinophilia, which is typically found in other hematopoietic malignancies with PDGFRA¬-containing fusions. We first detected an ETV6-SCFD2 fusion by targeted RNA sequencing in a patient with t(4;12)(q12;p13) who had previously been diagnosed with an ETV6-PDGFRA fusion by FISH analysis but failed to respond to imatinib. We then retrospectively identified four additional AML patients with t(4;12)(q12;p13) with apparent ETV6-PDGFRA fusions using chromosome and FISH analysis and applied targeted RNA sequencing to archival material. We again detected rearrangements between ETV6 and non-PDGFRA 4q12 genes including SCFD2, CHIC2 and GSX2. None of the three patients who received imatinib based on the incorrect assumption of an ETV6-PDGFRA fusion responded. Our findings highlight the importance of using a sequencing-based assay to confirm the presence of targetable gene fusions, particularly in genomic regions such as 4q12 with many clinically relevant genes that are too close to resolve by chromosome or FISH analysis. Finally, combining our data and review of the literature, we show that sequence-confirmed ETV6-PDGFRA fusions are typically found in eosinophilic disorders (3 of 3 cases), and patients with t(4;12)(q12;p13) without eosinophilia are found to have other 4q12 partners on sequencing (17 of 17 cases).

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 Spontaneous Remission in an Older Patient with RelapsedFLT3ITD Mutant AML

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Pankit Vachhani ◽  
Jason H. Mendler ◽  
Andrew Evans ◽  
George Deeb ◽  
Petr Starostik ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Tandem Duplication ◽  
Clinical Course ◽  
Spontaneous Remission ◽  
Rapid Progression ◽  
Older Patient ◽  
Internal Tandem Duplication ◽  
First Case ◽  
Short Overall Survival ◽  
Aggressive Clinical Course

Spontaneous remission (SR) of acute myeloid leukemia (AML) is a very rare phenomenon. AML characterized byFLT3internal tandem duplication (FLT3ITD) is typically associated with an aggressive clinical course with rapid progression, relapse, and short overall survival in the absence of transplantation. We report here the first case of SR ofFLT3ITD mutant AML in the literature. Our patient was an elderly woman with relapsedNPM1andFLT3ITD mutant AML whose disease underwent SR for a brief duration without precipitating cause. We review the potential immune mechanisms underlying SR in AML and discuss the implications for novel immunotherapeutic approaches forFLT3mutant AML.

scholarly journals BCR/ABL1 fluorescence in situ hybridization fusion signals on both copies of chromosome 22 in a Philadelphia-masked chronic myeloid leukemia case: implication for the therapy

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Silvia Soriani ◽  
Valentina Guido ◽  
Giambattista Bertani ◽  
Clara Cesana ◽  
Valentina Motta ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Chronic Myeloid Leukemia ◽  
Reciprocal Translocation ◽  
Myeloid Leukemia ◽  
Fusion Transcript ◽  
Chromosome 8 ◽  
Chromosome 22 ◽  
Fish Analysis ◽  
Ph Chromosome

The cytogenetic hallmark of Chronic Myeloid Leukemia (CML) is the presence of Philadelphia (Ph) chromosome, which results from a reciprocal translocation t(9;22)(q34;q11). In this report, we describe a CML patient with no evidence of Ph chromosome but trisomy of chromosome 8 as single cytogenetic abnormality and a typical e14a2 (b3a2) BCR-ABL1 fusion transcript. Fluorescence In Situ Hybridization (FISH) analysis revealed an uncommon signal pattern: the fusion signals were located on both copies of chromosome 22. During the course of the disease the appearance of the p.(Tyr315Ile) mutation was recorded. To the best of our knowledge this is the first Ph chromosome-negative CML case with e14a2 (b3a2) BCR-ABL1 transcript and p.(Tyr315Ile) mutation.

Comparison of Cytogenetics and Interphase Fluorescence In Situ Hybridization in Newly Diagnosed Ph+ Chronic Myeloid Leukemia Patients Treated with Imatinib Mesylate. A Study by the GIMEMA Working Party on CML. On Behalf of GWP on CML.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4857-4857
Author(s):  
Nicoletta Testoni ◽  
Simona Luatti ◽  
Chiara Nicci ◽  
Elena Montanari ◽  
Giulia Marzocchi ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Chronic Myeloid Leukemia ◽  
Fluorescence In Situ Hybridization ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Working Party ◽  
Chromosome 9 ◽  
Fish Analysis ◽  
Imatinib Treatment

Abstract To asses cytogenetic pattern of early diagnosed chronic phase chronic myeloid leukemia (CML) patients and to evaluate the role of either conventional (CC) and molecular cytogenetics in three multicentric studies, karyotype and interphase fluorescence in situ hybridization (FISH) analyses were performed in 372 enrolled patients between April 2004 and July 2005 by the GIMEMA CML Working Party (WP). Local investigator laboratories (25 labs) or WP reference labs (12 labs) performed both analyses. Cytogenetic examinations was performed at baseline; after 6 and 12 months of imatinib treatment; thereafter every 6 months and in case of failure or disease progression. At the baseline, 257 patients have been studied and 237 (92%) are valuable for both analyses (CC and FISH). Additional abnormalities in Ph+ clone have been observed in 12 patients (5%). Moreover, 18 (8%) cases showed variant Ph translocations and in 23 (10%) patients the derivative of chromosome 9 was deleted. As yet, cytogenetic response (CR) was evaluated in 188 samples and 156 cases were valuable (83%): 20 at 3 months, 101 at 6 months and 35 at 1 year of treatment. One hundred and eighteen (76%) patients achieved complete CR (CCR) established with more than 20 metaphases in 84 cases, meanwhile in 34 CCR cases the number of examined metaphases was lower. In the first group, 70/84 (83%) samples showed absence of bcr/abl rearrangement in FISH, meanwhile 13/84 (16%) carried a low rate of positive cells (1–5%) and the last one showed the rearrangement in 12% of cells. In the latter group, 23/34 (68%) didn’t show any rearrangement in FISH, in 8/34 (24%) the amount of Ph+ cells was low (1–5%), in 2 was higher (7% and 10%) and the last one carried an high rate (72%) of rearranged cells. In this latter case the RCC was evaluated on 10 metaphases. Twenty-three patients in major CR (MCR), but not in CCR, showed retention of persisting Ph+ cells ranging from 2 to 21% in CC study and from 2 to 16% in FISH analysis. Moreover we found a patient with 2% of Ph+ metaphases and 53% of Ph+ cells in FISH: in this case the CC evaluation was established with 10 metaphases. We can suggest there was a good correlation between cytogenetic and FISH tests in terms of the kinetics of disappearance of the bcr/abl rearrangement. FISH is a reliable method to reveal submicroscopic deletions and to monitor the size of the Ph + clone in treated CML patients. However, a good CC analysis remains an excellent approach to the evaluation of response to Imatinib. Moreover it can detect the emergence of other abnormalities in Ph positive or negative clone.

Gain of chromosome 3q is an early and consistent genetic aberration in carcinomas of the vulva

2005 ◽  
Vol 15 (1) ◽  
pp. 120-126 ◽  
Author(s):  
P. Stoltzfus ◽  
K. Heselmeyer-Haddad ◽  
J. Castro ◽  
N. White ◽  
C. Silfverswärd ◽  
...  
Keyword(s):  
Precancerous Lesions ◽  
Immunohistochemical Analysis ◽  
Fold Increase ◽  
Chromosome 3 ◽  
Fish Analysis ◽  
Archival Material ◽  
Genetic Aberration ◽  
Invasive Capacity ◽  
Multicolor Fluorescence

The aim was to determine whether specific gains of chromosome 3q and laminin-5γ2-chain expression can improve early detection of invasive capacity in precancerous and squamous cell carcinoma of the vulva (VSCC). Six VSCC and three precancerous lesions were studied. Multicolor fluorescence in situ hybridization (FISH) probe sets were applied to nuclei suspensions prepared from archival material using the Hedley method. The probe panel consists of the centromers of chromosome 7, chromosome 3, and the TERC gene residing on the long arm of chromosome 3. Laminin-5γ2-chain immunohistochemical analysis was performed on corresponding specimens and was expressed only in the VSCC. The genome-specific FISH analysis revealed 3q amplification in 43% of the nuclei analyzed for the VSCC and 22% of the nuclei for the precancerous lesions. Low-level 3q amplifications were found in precancerous lesions with an average fold increase of 1.15 for 3q. The invasive lesions showed higher average fold increases for 3q, averaging 1.32. Laminin-5γ2-chain protein was expressed only in VSCC, whereas 3q gains were observed both in precancerous lesions and in VSCC, indicating that gain of chromosome 3q is an early and consistent event during carcinogenesis of VSCC.

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 Acute Leukemia of Ambiguous Lineage with a Rare Abnormality Del17p by FISH Analysis

2020 ◽  
Vol 5 (2) ◽  
pp. 79-82
Author(s):  
Naeem Abbas ◽  
◽  
Samra Waheed ◽  
Aisha Jamal ◽  
Ali Saleem ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Myeloid Leukemia ◽  
World Health ◽  
Fish Analysis ◽  
Rare Entity ◽  
Therapeutic Approaches ◽  
The World ◽  
Health Organization ◽  
Acute Myeloid

Abstract: The World Health Organization (WHO) has categorized acute undifferentiated leukemia (AUL) as a rare subtype of acute leukemia of ambiguous lineage (ALAL). The prognosis of AUL is considered poor and it expresses no known lineage-specific markers. In majority of the cases, AUL has been associated with karyotypic abnormalities, most commonly deletion 5q and complex karyotype. Deletion 17p correlation with acute myeloid leukemia and myelodysplastic syndome has been previously established and is associated with poorer outcomes. Herein we are reporting a case of forty years old male who was referred to National institute of blood diseases and bone marrow transplantation with complains of fever, multiple neck swellings, and early satiety and was diagnosed as Acute Undifferentiated Leukemia along with deletion 17p. This is a rare entity and can aid in further diagnostic and therapeutic approaches. Keywords: Acute undifferentiated leukemia, Deletion 17p, Flourescnece in situ hybridization, Allogeneic haematopoetic stem cell transplantation, Flow cytometry.

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 Early Complete Molecular Response to First-Line Nilotinib in Two Patients with Chronic Myeloid Leukemia Carrying the p230 Transcript

2013 ◽  
Vol 2013 ◽  
pp. 1-2 ◽  
Author(s):  
Marianna Greco ◽  
Giovanni Caocci ◽  
Giorgio La Nasa
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Clinical Course ◽  
Fusion Gene ◽  
Molecular Response ◽  
First Line ◽  
Frontline Treatment ◽  
Aggressive Clinical Course ◽  
Complete Molecular Response

Chronic myeloid leukemia (CML) with the rare fusion gene e19a2, encoding a p230 protein, has been described in patients with typical or rather aggressive clinical course. Although tyrosine kinase inhibitors (TKIs) induce a substantial cytogenetic and molecular response in all phases of CML, a minority of p230 positive patients have been treated with TKIs. We report two cases of CML patients carrying the p230 transcript, who achieved fast and deep complete molecular response (CMR) after frontline treatment with nilotinib. Our results suggest the use of nilotinib as frontline agent for the treatment of this CML variant.

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