Evaluation of multiprobe fluoresence in-situ hybridization panel in the detection of common chromosomal abnormalities of acute myeloid leukemia

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.

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Early Fluorescence in situ Hybridization Assessment during Acute Myeloid Leukemia Induction Chemotherapy

Acta Haematologica ◽

10.1159/000487879 ◽

2018 ◽

Vol 139 (3) ◽

pp. 171-175

Author(s):

Robert Schneidewend ◽

Paul Hosking ◽

Ruta Brazauskas ◽

Jess Peterson ◽

Carlie Beaudin ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Induction Chemotherapy ◽

Myeloid Leukemia ◽

Acute Myeloid

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Prognostic Value of Metaphase-Fluorescence In Situ Hybridization in Follow-up of Patients With Acute Myeloid Leukemia in Remission

Blood ◽

10.1182/blood.v89.9.3330 ◽

1997 ◽

Vol 89 (9) ◽

pp. 3330-3334 ◽

Cited By ~ 13

Author(s):

Wa'el El-Rifai ◽

Tapani Ruutu ◽

Erkki Elonen ◽

Liisa Volin ◽

Sakari Knuutila

Keyword(s):

Acute Myeloid Leukemia ◽

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Myeloid Leukemia ◽

Allogeneic Bone Marrow Transplantation ◽

Leukemic Cells ◽

Allogeneic Bone ◽

Abnormal Cells ◽

Acute Myeloid

Abstract The presence of residual leukemic cells was studied using metaphase-fluorescence in situ hybridization (FISH) in 22 patients with acute myeloid leukemia treated with chemotherapy only or chemotherapy followed by allogeneic bone marrow transplantation. The patients were followed up during their complete remission (CR) for 4 to 108 months (median, 21 months). A total of 88 BM samples was studied. In most of the samples more than 1,000 metaphase cells were analyzed. Residual leukemic cells were detected in 9 of 22 patients (41%). All patients who had an increasing and/or persisting level of abnormal cells in two or more subsequent samples or whose initial samples contained more than 1% of abnormal cells relapsed with one exception, in whom the later subsequent samples showed disappearance of abnormal cells. The time span before the first positive sample seems to be insignificant with regard to the outcome of relapse. Absence or single occurrence of abnormal cells followed by their disappearance was in agreement with CR in all the cases (16 patients). Our results indicate that metaphase-FISH is a reliable tool in the quantitation of residual leukemic cells and provides valuable prognostic information for patients with AML.

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

Blood ◽

10.1182/blood.v106.11.4504.4504 ◽

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.

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A fluorescence in situ hybridization-based screen allows rapid detection of adverse cytogenetic alterations in patients with acute myeloid leukemia

Genes Chromosomes and Cancer ◽

10.1002/gcc.22466 ◽

2017 ◽

Vol 56 (8) ◽

pp. 632-638

Author(s):

Nadine Sandhöfer ◽

Klaus H. Metzeler ◽

Purvi M. Kakadia ◽

Zlatana Pasalic ◽

Wolfgang Hiddemann ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Rapid Detection ◽

Myeloid Leukemia ◽

Acute Myeloid

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Hyperdiploid acute myeloid leukemia Relationship between blast size and karyotype demonstrated by fluorescence in situ hybridization

Cancer Genetics and Cytogenetics ◽

10.1016/s0165-4608(95)00027-5 ◽

1995 ◽

Vol 83 (1) ◽

pp. 1-4 ◽

Cited By ~ 11

Author(s):

Y.L. Kwong ◽

K.F. Wong

Keyword(s):

Acute Myeloid Leukemia ◽

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Myeloid Leukemia ◽

Acute Myeloid

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Two rare cases of acute myeloid leukemia with t(8;16)(p11.2;p13.3) and 1q duplication: case presentation and literature review

10.21203/rs.3.rs-24639/v2 ◽

2020 ◽

Author(s):

Meng Liu ◽

Yuan Ren ◽

Xianfu Wang ◽

Xianglan Lu ◽

Ming Li ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Chromosomal Abnormalities ◽

Chromosome Analysis ◽

Recurrent Event ◽

Chromosome 1 ◽

Comparative Genome Hybridization ◽

Array Comparative Genome Hybridization ◽

Acute Myeloid

Abstract Background: Acute myeloid leukemia (AML) is a complex hematological disease characterized by genetic and clinical heterogeneity. The identification and understanding of chromosomal abnormalities are important for the diagnosis and management of AML patients. Compared to recurrent chromosomal translocations in AML, t(8;16)(p11.2;p13.3) can be found in any age group, but is very rare and typically associated with poor prognosis. Methods: Conventional cytogenetic studies were performed among 1,824 AML patients from our oncology database in the last 20 years. Fluorescence in situ hybridization (FISH) was carried out to demonstrate the translocation fusion. Array comparative genome hybridization (aCGH) was carried out to further characterize the duplication of chromosomes.Results: We identified three AML patients with t(8;16)(p11.2;p13.3) by chromosome analysis. Two of the three patients with additional 1q duplication were detected by FISH and aCGH. aCGH characterized a 46.7 Mb and 49.9 Mb gain of chromosome 1 at bands q32.1q44 in these two patients, respectively. One patient achieved a complete remission (CR) but relapsed three months later. The other patient never experienced a CR and died two years after diagnosis. Conclusion: 1q duplication were detected in two of three AML patients with t(8;16)(p11.2;p13.3), suggesting that 1q duplication can be a recurrent event in AML patients with t(8;16). In concert with the findings of previous studies of similar patients, our work suggests that 1q duplication may also be an unfavorable prognostic factor of the disease.

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