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Article ; Online: Fluorescence In Situ Hybridization (FISH) in Multiple Myeloma.

Tian, Erming

Methods in molecular biology (Clifton, N.J.)

2018 Volume 1792, Page(s) 55–69

Abstract: The application of fluorescence in situ hybridization (FISH) technology in diagnosis and molecular classification of cancer-risk has become an essential tool in the proceeding of personalized therapy. In multiple myeloma, the precise FISH detection of ... ...

Abstract	The application of fluorescence in situ hybridization (FISH) technology in diagnosis and molecular classification of cancer-risk has become an essential tool in the proceeding of personalized therapy. In multiple myeloma, the precise FISH detection of numerical and structural genetic aberrations can be carried out on metaphase chromosome spreads, interphase nuclei, and formalin fixed paraffin-embedded (FFPE) tissues. To dissect highly complex cancer genomes, a broad variety of novel DNA probes, which outpace supplies from commercial resources on the market, are also crucial to the advanced translational researches. Here, we provide the protocols for the creation of custom-made DNA probes and for conducting hybridizations on various targeting cells and tissues.
MeSH term(s)	Biomarkers, Tumor ; Bone Marrow/metabolism ; Bone Marrow/pathology ; DNA Probes ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence/methods ; Interphase/genetics ; Metaphase/genetics ; Multiple Myeloma/diagnosis ; Multiple Myeloma/genetics
Chemical Substances	Biomarkers, Tumor ; DNA Probes
Language	English
Publishing date	2018-05-23
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-7865-6_5
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Article ; Online: Innate Biomineralization.

Tian, Erming / Watanabe, Fumiya / Martin, Betty / Zangari, Maurizio

International journal of molecular sciences

2020 Volume 21, Issue 14

Abstract: In vertebrates, biomineralization is a feature considered unique to mature osteoblasts and odontoblasts by which they synthesize hydroxyapatite (HAP), which is deposited in the collagen matrix to construct endoskeleton. For many decades, the mechanisms ... ...

Abstract	In vertebrates, biomineralization is a feature considered unique to mature osteoblasts and odontoblasts by which they synthesize hydroxyapatite (HAP), which is deposited in the collagen matrix to construct endoskeleton. For many decades, the mechanisms that modulate differentiation and maturation of these specialized cells have been sought as a key to understanding bone-remodeling defects. Here, we report that biomineralization is an innate ability of all mammalian cells, irrespective of cell type or maturation stage. This innate biomineralization is triggered by the concomitant exposure of living cells to three indispensable elements: calcium ion, phosphoester salt, and alkaline phosphatase. Any given somatic cell, including undifferentiated mononuclear cells, can undergo a biomineralization process to produce calcium-phosphate agglomerates. The biologically generated minerals under such conditions are composed of genuine HAP crystallites of Ca
MeSH term(s)	Alkaline Phosphatase/metabolism ; Animals ; Biomineralization/physiology ; Bone and Bones/metabolism ; Bone and Bones/physiology ; Calcium Phosphates/metabolism ; Cell Differentiation/physiology ; Cell Line ; Cell Line, Tumor ; Collagen/metabolism ; Durapatite/metabolism ; HEK293 Cells ; HL-60 Cells ; HeLa Cells ; Humans ; K562 Cells ; MCF-7 Cells ; Mammals/metabolism ; Mammals/physiology ; Mice ; NIH 3T3 Cells ; Odontoblasts/metabolism ; Odontoblasts/physiology ; Osteoblasts/metabolism ; Osteoblasts/physiology ; PC-3 Cells ; THP-1 Cells ; U937 Cells
Chemical Substances	Calcium Phosphates ; Collagen (9007-34-5) ; Durapatite (91D9GV0Z28) ; calcium phosphate (97Z1WI3NDX) ; Alkaline Phosphatase (EC 3.1.3.1)
Language	English
Publishing date	2020-07-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21144820
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Article ; Online: Concomitant deletion of the short arm (del(1p13.3)) and amplification or gain (1q21) of chromosome 1 by fluorescence in situ hybridization are associated with a poor clinical outcome in multiple myeloma.

Mohan, Meera / Gong, Zimu / Ashby, Timothy Cody / Al Hadidi, Samer / Thanendrarajan, Sharmilan / Schinke, Carolina / Alapat, Daisy / Shaughnessy, John D / Zhan, Fenghuang / van Rhee, Frits / Sawyer, Jeffery R / Tian, Erming / Zangari, Maurizio

Cancer

2023 Volume 129, Issue 16, Page(s) 2491–2498

Abstract: Background: Chromosome 1 abnormalities in multiple myeloma (MM) are increasingly recognized as high risk-defining features. The authors report the prognostic value of del(1p13.3) by fluorescence in situ hybridization (FISH) at enrollment in subjects ... ...

Abstract	Background: Chromosome 1 abnormalities in multiple myeloma (MM) are increasingly recognized as high risk-defining features. The authors report the prognostic value of del(1p13.3) by fluorescence in situ hybridization (FISH) at enrollment in subjects treated on total therapy clinical trials 2-6. Methods: FISH probes were generated from specific BAC DNA clones for the AHCYL1 gene locus (1p13.3) and the CKS1B locus (1q21). Results: A total of 1133 patients were included in this analysis. Although del(1p13.3) was detected in 220 (19.4%) patients, 1q21gain or 1q21amp were observed in 300 (26.5%) and 150 (13.2%) patients, respectively. Concomitant del(1p13.3) with 1q21 gain or amp was observed in 65 (5.7%) and 29 (2.5%) patients, respectively. There was enrichment of high-risk features such as International Staging System (ISS) stage 3 disease and gene expression profiling (GEP)70 high risk (HR) in the group with del(1p13.3). Presence of del(1p13.3) confers inferior progression-free survival (PFS) and overall survival (OS). On multivariate analysis, the presence of ISS stage 3 disease, GEP70 HR, 1q21gain, and 1q21amp were independent predictors of PFS or OS. Conclusions: The PFS and OS of patients with combined abnormalities of del (1p13.3)/1q21gain or amp was significantly worse compared to del(1p13.3) alone and 1q21gain or 1q21 amp alone, which identifies a subset of patients with poor clinical outcomes.
MeSH term(s)	Humans ; Multiple Myeloma/therapy ; In Situ Hybridization, Fluorescence ; Chromosomes, Human, Pair 1/genetics ; Chromosome Aberrations ; Prognosis ; Chromosome Deletion
Language	English
Publishing date	2023-06-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1429-1
ISSN	1097-0142 ; 0008-543X ; 1934-662X
ISSN (online)	1097-0142
ISSN	0008-543X ; 1934-662X
DOI	10.1002/cncr.34895
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Article ; Online: Identification of novel breakpoints for locus- and region-specific translocations in 293 cells by molecular cytogenetics before and after irradiation.

Binz, Regina L / Tian, Erming / Sadhukhan, Ratan / Zhou, Daohong / Hauer-Jensen, Martin / Pathak, Rupak

Scientific reports

2019 Volume 9, Issue 1, Page(s) 10554

Abstract: The human kidney embryonic 293 cell line (293 cells) is extensively used in biomedical and pharmaceutical research. These cells exhibit a number of numerical and structural chromosomal anomalies. However, the breakpoints responsible for these structural ... ...

Abstract	The human kidney embryonic 293 cell line (293 cells) is extensively used in biomedical and pharmaceutical research. These cells exhibit a number of numerical and structural chromosomal anomalies. However, the breakpoints responsible for these structural chromosomal rearrangements have not been comprehensively characterized. In addition, it is not known whether chromosomes with structural rearrangement are more sensitive to external toxic agents, such as ionizing radiation. We used G-banding, spectral karyotyping (SKY), and locus- and region-specific fluorescence in situ hybridization (FISH) probes designed in our lab or obtained from commercial vendor to address this gap. Our G-banding analysis revealed that the chromosome number varies from 66 to 71, with multiple rearrangements and partial additions and deletions. SKY analysis confirmed 3 consistent rearrangements, two simple and one complex in nature. Multicolor FISH analysis identified an array of breakpoints responsible for locus- and region-specific translocations. Finally, SKY analysis revealed that radio-sensitivity of structurally rearranged chromosomes is dependent on radiation dose. These findings will advance our knowledge in 293 cell biology and will enrich the understanding of radiation biology studies.
MeSH term(s)	Chromosome Aberrations ; Chromosome Banding ; Chromosome Breakpoints/radiation effects ; Chromosome Painting ; Cytogenetics ; Gene Rearrangement/radiation effects ; HEK293 Cells ; Humans ; Radiation Tolerance/genetics ; Spectral Karyotyping ; Translocation, Genetic/radiation effects
Language	English
Publishing date	2019-07-22
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-47002-0
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Article ; Online: Daratumumab in high-risk relapsed/refractory multiple myeloma patients: adverse effect of chromosome 1q21 gain/amplification and GEP70 status on outcome.

Mohan, Meera / Weinhold, Niels / Schinke, Carolina / Thanedrarajan, Sharmilan / Rasche, Leo / Sawyer, Jeffrey R / Tian, Erming / van Rhee, Frits / Zangari, Maurizio

British journal of haematology

2019 Volume 189, Issue 1, Page(s) 67–71

Abstract: Gain of chromosome 1q21 and the gene expression-based GEP70 risk score are established prognostic markers for newly diagnosed Multiple Myeloma (MM) patients. Here we addressed the prognostic impact of these two markers in 81 relapsed/refractory (RR) MM ... ...

Abstract	Gain of chromosome 1q21 and the gene expression-based GEP70 risk score are established prognostic markers for newly diagnosed Multiple Myeloma (MM) patients. Here we addressed the prognostic impact of these two markers in 81 relapsed/refractory (RR) MM patients treated with the CD38-antibody daratumumab. Fluorescence in situ hybridization for 1q21 was performed at initial presentation, while the GEP70 score was determined at initial presentation and prior to daratumumab treatment. While the GEP70 at initial presentation showed a trend for inferior survival, the GEP70 collected prior to daratumumab treatment was significantly associated with poor outcome (P < 0·05). The worst outcome was seen for patients who were positive for gain(1q) and classified as GEP70 high risk prior to daratumumab [progression-free (PFS) and overall survival (OS) of 0·3 years (95% CI: 0·15-1·4 years) and 0·8 years (95% CI: 0·5-1·9 years) respectively], while the median PFS and OS were not reached by patients without gain(1q) and GEP70 low-risk status. In conclusion, gain(1q) and the GEP70 are powerful prognostic markers for RR MM patients treated with daratumumab, and patients classified as high risk according to these markers experience shorter treatment response.
MeSH term(s)	Adult ; Aged ; Antibodies, Monoclonal/administration & dosage ; Chromosomes, Human, Pair 1/genetics ; Disease-Free Survival ; Female ; Follow-Up Studies ; Gene Amplification ; Humans ; Male ; Middle Aged ; Multiple Myeloma/drug therapy ; Multiple Myeloma/genetics ; Multiple Myeloma/mortality ; Risk Assessment ; Survival Rate
Chemical Substances	Antibodies, Monoclonal ; daratumumab (4Z63YK6E0E)
Language	English
Publishing date	2019-12-09
Publishing country	England
Document type	Journal Article
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.16292
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Article ; Online: Persistent bone marrow minimal residual disease as a "high-risk" disease feature in multiple myeloma.

Mohan, Meera / Szabo, Aniko / Yarlagadda, Naveen / Gundarlapalli, Sravani / Thanendrarajan, Sharmilan / Kendrick, Samantha / Schinke, Carolina / Alapat, Daisy / Sawyer, Jeffrey / Tian, Erming / Tricot, Guido / van Rhee, Frits / Zangari, Maurizio

American journal of hematology

2021 Volume 96, Issue 9, Page(s) E341–E344

MeSH term(s)	Aged ; Bone Marrow/pathology ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma/diagnosis ; Multiple Myeloma/pathology ; Neoplasm, Residual/diagnosis ; Neoplasm, Residual/pathology ; Prognosis ; Survival Analysis
Language	English
Publishing date	2021-06-29
Publishing country	United States
Document type	Letter
ZDB-ID	196767-8
ISSN	1096-8652 ; 0361-8609
ISSN (online)	1096-8652
ISSN	0361-8609
DOI	10.1002/ajh.26255
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Zs.A 1251: Show issues

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Article ; Online: Bone remineralization of lytic lesions in multiple myeloma - The Arkansas experience.

Mohan, Meera / Kumar, Manoj / Samant, Rohan / Van Hemert, Rudy / Tian, Erming / Desai, Shivang / van Rhee, Frits / Thanendrarajan, Sharmilan / Schinke, Carolina / Suva, Larry J / Sharma, Shobhit / Milad, Mohamed / Kendrick, Samantha / Zangari, Maurizio

Bone

2021 Volume 146, Page(s) 115876

Abstract: Multiple myeloma (MM) patients frequently present with extensive osteolytic bone lesions. However, the impact of myeloma treatment on focal lytic lesion remineralization has not been extensively studied. In this study, the effect of anti-myeloma ... ...

Abstract	Multiple myeloma (MM) patients frequently present with extensive osteolytic bone lesions. However, the impact of myeloma treatment on focal lytic lesion remineralization has not been extensively studied. In this study, the effect of anti-myeloma treatment on the extent of bone remineralization was examined and potential mediators identified. Newly diagnosed MM patients enrolled in the Total Therapy 4 and 5 (TT4; n = 231, TT5; n = 64) protocols were longitudinally evaluated for changes in radiological parameters for a median of 6.1 years. Bone remineralization was defined as a sclerotic CT change within the lytic lesion and quantified as a percentage of remineralization, using the initial lesion size as a reference. Such changes were correlated to clinical and biochemical parameters, and the gene expression profile of bone marrow biopsy. Overall, remineralization occurred in 72% of patients (213/295). Of those patients that experienced remineralization, 36% (107/295) achieved at least 25% of bone remineralization. Patients with high-risk disease defined by gene expression profile signature (GEP70 ≥ 0.66) experienced significant remineralization compared to low-risk MM. Female patients were also more likely to experience bone remineralization and in a shorter median time (2.0 vs. 3.3 y). Factors such as serum alkaline phosphatase along with high levels of RUNX2 and SOX4 gene expression correlated with increasing extent of bone remineralization. This analysis demonstrated significant remineralization of lytic lesions in MM patients treated on TT clinical trials. While the underlying mechanism remains elusive these findings support the hypothesis that patient baseline bone-related factors play a fundamental role in the skeletal repair of bone lesions in MM that provide new opportunities for improving patient outcomes.
MeSH term(s)	Arkansas ; Bone Diseases ; Bone Marrow ; Bone and Bones ; Female ; Humans ; Multiple Myeloma/drug therapy ; SOXC Transcription Factors
Chemical Substances	SOX4 protein, human ; SOXC Transcription Factors
Language	English
Publishing date	2021-02-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	632515-4
ISSN	1873-2763 ; 8756-3282
ISSN (online)	1873-2763
ISSN	8756-3282
DOI	10.1016/j.bone.2021.115876
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Article ; Online: An Evaluation of Gene Set Analysis for Biomarker Discovery with Applications to Myeloma Research

Qu, Pingping / Tian, Erming / Barlogie, Bart / Morgan, Gareth / Crowley, John

Frontiers of Biostatistical Methods and Applications in Clinical Oncology

Abstract: In this paper, we evaluate 15 methods for gene set analysis in microarray classification problems. We employ four datasets from myeloma research and three types of biological gene sets, encompassing a total of 12 scenarios. Taking a two-step approach, we ...

Abstract	In this paper, we evaluate 15 methods for gene set analysis in microarray classification problems. We employ four datasets from myeloma research and three types of biological gene sets, encompassing a total of 12 scenarios. Taking a two-step approach, we first identify important genes within gene sets to create summary gene set scores, we then construct predictive models using the gene set scores as predictors. We propose two powerful linear methods in addition to the well-known SuperPC method for calculating scores. By comparing the 15 gene set methods with methods used in individual-gene analysis, we conclude that, overall, the gene set analysis approach provided more accurate predictions than the individual-gene analysis.
Keywords	covid19
Publisher	PMC
Document type	Article ; Online
DOI	10.1007/978-981-10-0126-0_25
Database	COVID19

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Article ; Online: Clinical implications of loss of bone marrow minimal residual disease negativity in multiple myeloma.

Mohan, Meera / Kendrick, Samantha / Szabo, Aniko / Yarlagadda, Naveen / Atwal, Dinesh / Pandey, Yadav / Roy, Arya / Parikh, Richa / Lopez, James / Thanendrarajan, Sharmilan / Schinke, Carolina / Alapat, Daisy / Sawyer, Jeffrey / Tian, Erming / Tricot, Guido / van Rhee, Frits / Zangari, Maurizio

Blood advances

2021 Volume 6, Issue 3, Page(s) 808–817

Abstract: Multiple myeloma (MM) patients frequently attain a bone marrow (BM) minimal residual disease (MRD) negativity status in response to treatment. We identified 568 patients who achieved BM MRD negativity following autologous stem cell transplantation (ASCT) ...

Abstract	Multiple myeloma (MM) patients frequently attain a bone marrow (BM) minimal residual disease (MRD) negativity status in response to treatment. We identified 568 patients who achieved BM MRD negativity following autologous stem cell transplantation (ASCT) and maintenance combination therapy with an immunomodulatory agent and a proteasome inhibitor. BM MRD was evaluated by next-generation flow cytometry (sensitivity of 10-5 cells) at 3- to 6-month intervals. With a median follow-up of 9.9 years from diagnosis (range, 0.4-30.9), 61% of patients maintained MRD negativity, whereas 39% experienced MRD conversion at a median of 6.3 years (range, 1.4-25). The highest risk of MRD conversion occurred within the first 5 years after treatment and was observed more often in patients with abnormal metaphase cytogenetic abnormalities (95% vs 84%; P = .001). MRD conversion was associated with a high risk of relapse and preceded it by a median of 1.0 years (range, 0-4.9). However, 27% of MRD conversion-positive patients had not yet experienced a clinical relapse, with a median follow-up of 9.3 years (range, 2.2-21.2). Landmark analyses using time from ASCT revealed patients with MRD conversion during the first 3 years had an inferior overall and progression-free survival compared with patients with sustained MRD negativity. MRD conversion correctly predicted relapse in 70%, demonstrating the utility of serial BM MRD assessment to complement standard laboratory and imaging to make informed salvage therapy decisions.
MeSH term(s)	Bone Marrow ; Hematopoietic Stem Cell Transplantation ; Humans ; Multiple Myeloma/drug therapy ; Multiple Myeloma/therapy ; Neoplasm Recurrence, Local ; Neoplasm, Residual/diagnosis ; Transplantation, Autologous ; Treatment Outcome
Language	English
Publishing date	2021-12-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2021005822
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Article ; Online: An acquired high-risk chromosome instability phenotype in multiple myeloma: Jumping 1q Syndrome.

Sawyer, Jeffrey R / Tian, Erming / Walker, Brian A / Wardell, Christopher / Lukacs, Janet L / Sammartino, Gael / Bailey, Clyde / Schinke, Carolina D / Thanendrarajan, Sharmilan / Davies, Faith E / Morgan, Gareth J / Barlogie, Bart / Zangari, Maurizio / van Rhee, Frits

Blood cancer journal

2019 Volume 9, Issue 8, Page(s) 62

Abstract: Patients with multiple myeloma (MM) accumulate adverse copy number aberrations (CNAs), gains of 1q21, and 17p deletions during disease progression. A subset of these patients develops heightened 1q12 pericentromeric instability and jumping translocations ...

Abstract	Patients with multiple myeloma (MM) accumulate adverse copy number aberrations (CNAs), gains of 1q21, and 17p deletions during disease progression. A subset of these patients develops heightened 1q12 pericentromeric instability and jumping translocations of 1q12 (JT1q12), evidenced by increased copy CNAs of 1q21 and losses in receptor chromosomes (RC). To understand the progression of these aberrations we analyzed metaphase cells of 50 patients with ≥4 CNAs of 1q21 by G-banding, locus specific FISH, and spectral karyotyping. In eight patients with ≥5 CNAs of 1q21 we identified a chromosome instability phenotype similar to that found in ICF syndrome (immunodeficiency, centromeric instability, and facial anomalies). Strikingly, the acquired instability phenotype identified in these patients demonstrates the same transient structural aberrations of 1q12 as those found in ICF syndrome, suggesting similar underlying pathological mechanisms. Four types of clonal aberrations characterize this phenotype including JT1q12s, RC deletions, 1q12-21 breakage-fusion-bridge cycle amplifications, and RC insertions. In addition, recurring transient aberrations include 1q12 decondensation and breakage, triradials, and 1q micronuclei. The acquired self-propagating mobile property of 1q12 satellite DNA drives the continuous regeneration of 1q12 duplication/deletion events. For patients demonstrating this instability phenotype, we propose the term "Jumping 1q Syndrome."
MeSH term(s)	Chromosomal Instability ; Chromosomes, Human, Pair 1 ; Disease Progression ; Humans ; In Situ Hybridization, Fluorescence/methods ; Multiple Myeloma/diagnosis ; Multiple Myeloma/genetics ; Multiple Myeloma/pathology ; Prognosis ; Syndrome ; Translocation, Genetic
Language	English
Publishing date	2019-08-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	2600560-8
ISSN	2044-5385 ; 2044-5385
ISSN (online)	2044-5385
ISSN	2044-5385
DOI	10.1038/s41408-019-0226-4
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