Interphase fluorescence in situ hybridization in multiple myeloma and monoclonal gammopathy of undetermined significance without and with positive plasma cell identification: analysis of 192 cases from the Region of Southern Denmark

Abstract We investigated whether interleukin-1β (IL-1β) is differentially expressed in plasma cells from monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) patients because IL-1β appears to play a major role in the development of lytic bone lesions, the major clinical feature distinguishing MGUS from myeloma. In situ hybridization (ISH) for IL-1β was performed using bone marrow aspirates from 51 MM, 7 smoldering MM, 21 MGUS, and 5 normal control samples. Using the ISH technique IL-1β mRNA was detectable in the plasma cells from 49 of 51 patients with active myeloma and 7 of 7 patients with smoldering myeloma. In contrast, 5 of 21 patients with MGUS and 0 of 5 normal controls had detectable IL-1β message. Bone lesions were present in 40 of the 51 MM patients analyzed, and all 40 patients had IL-1β mRNA by ISH. These results show that greater than 95% of MM patients but less than 25% of MGUS patients are positive for IL-1β production. In the future, continued follow-up of IL-1β positive and negative MGUS patients should determine whether aberrant expression of plasma cell IL-1β is predictive of those MGUS patients that will eventually progress to active myeloma.

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Cytogenetic and fluorescence in situ hybridization studies in 60 patients with multiple myeloma and plasma cell leukemia

Cancer Genetics and Cytogenetics ◽

10.1016/s0165-4608(03)00233-4 ◽

2004 ◽

Vol 148 (1) ◽

pp. 71-76 ◽

Cited By ~ 13

Author(s):

Elisabet Lloveras ◽

Isabel Granada ◽

Lurdes Zamora ◽

Blanca Espinet ◽

Lourdes Florensa ◽

...

Keyword(s):

Multiple Myeloma ◽

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Plasma Cell ◽

Plasma Cell Leukemia ◽

Cell Leukemia

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Interphase fluorescence in situ hybridization identifies chromosomal abnormalities in plasma cells from patients with monoclonal gammopathy of undetermined significance

Blood ◽

10.1182/blood.v86.10.3915.bloodjournal86103915 ◽

1995 ◽

Vol 86 (10) ◽

pp. 3915-3921 ◽

Cited By ~ 102

Author(s):

J Drach ◽

J Angerler ◽

J Schuster ◽

C Rothermundt ◽

R Thalhammer ◽

...

Keyword(s):

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Monoclonal Gammopathy ◽

Plasma Cells ◽

Chromosomal Abnormalities ◽

Early Stage ◽

Chromosome 11 ◽

Bone Marrow Plasma ◽

Undetermined Significance

Karyotypic studies in patients with monoclonal gammopathy of undetermined significance (MGUS) have been hampered by a low percentage of bone marrow plasma cells (BMPC), which are predominantly nonproliferating. By combining cytomorphology and interphase fluorescence in situ hybridization (FISH) we investigated whether or not chromosomal abnormalities occur in BMPC from patients with MGUS. Studying chromosomes 3, 7, 11, and 18, which we found to be frequently aneuploid by FISH in multiple myeloma (MM), we observed three hybridization signals for one of these chromosomes 3 were most common, occurring in 38.9% of patients, followed by gains of chromosomes 11 (25%), 7 (16.7%), and 18 (5.6%) Among BMPC, the frequency of aneuploid cells was 18.9% +/- 13.9% (mean +/- SD) for chromosome 3, 22.3% +/- 9.2% for chromosome 11, 23.2% +/- 22.0% for chromosome 7, and 6.1% +/- 2.3% for chromosome 18. In five patients, chromosomal abnormalities were shown to be restricted to BMPC expressing cytoplasmic immunoglobulins corresponding to the serum paraprotein. No gain of hybridization signals was observed in normal and reactive plasma cells. In one patient with MGUS, metaphase cytogenetics revealed one abnormal metaphase with 47, XY, +4, and trisomy 4 was also demonstrated in a subpopulation of BMPC by interphase FISH. FISH results from patients with MGUS and newly diagnosed MM at stage IA (n = 14) indicated that aberrations involving > or = 2 chromosomes occurred significantly more often in early stage MM (P < .01). With respect to clinical and laboratory features, MGUS patients with and without chromosomal abnormalities were indistinguishable. Our results indicate that MGUS already has the chromosomal characteristics of a plasma cell malignancy.

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Significant increase of CKS1B amplification from monoclonal gammopathy of undetermined significance to multiple myeloma and plasma cell leukaemia as demonstrated by interphase fluorescence in situ hybridisation

British Journal of Haematology ◽

10.1111/j.1365-2141.2006.06237.x ◽

2006 ◽

Vol 134 (6) ◽

pp. 613-615 ◽

Cited By ~ 24

Author(s):

Hong Chang ◽

Joanna Yeung ◽

Wei Xu ◽

Yi Ning ◽

Bruce Patterson

Keyword(s):

Multiple Myeloma ◽

Plasma Cell ◽

Monoclonal Gammopathy ◽

In Situ Hybridisation ◽

Cell Leukaemia ◽

Fluorescence In Situ Hybridisation ◽

Plasma Cell Leukaemia ◽

Undetermined Significance

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Comparison of Interleukin-1β Expression by In Situ Hybridization in Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma

Blood ◽

10.1182/blood.v93.1.300.401k36_300_305 ◽

1999 ◽

Vol 93 (1) ◽

pp. 300-305 ◽

Cited By ~ 1

Author(s):

Martha Q. Lacy ◽

Kathleen A. Donovan ◽

Julie K. Heimbach ◽

Gregory J. Ahmann ◽

John A. Lust

Keyword(s):

Multiple Myeloma ◽

In Situ Hybridization ◽

Monoclonal Gammopathy ◽

Plasma Cells ◽

Interleukin 1Β ◽

Clinical Feature ◽

Bone Lesions ◽

Aberrant Expression ◽

Undetermined Significance

We investigated whether interleukin-1β (IL-1β) is differentially expressed in plasma cells from monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) patients because IL-1β appears to play a major role in the development of lytic bone lesions, the major clinical feature distinguishing MGUS from myeloma. In situ hybridization (ISH) for IL-1β was performed using bone marrow aspirates from 51 MM, 7 smoldering MM, 21 MGUS, and 5 normal control samples. Using the ISH technique IL-1β mRNA was detectable in the plasma cells from 49 of 51 patients with active myeloma and 7 of 7 patients with smoldering myeloma. In contrast, 5 of 21 patients with MGUS and 0 of 5 normal controls had detectable IL-1β message. Bone lesions were present in 40 of the 51 MM patients analyzed, and all 40 patients had IL-1β mRNA by ISH. These results show that greater than 95% of MM patients but less than 25% of MGUS patients are positive for IL-1β production. In the future, continued follow-up of IL-1β positive and negative MGUS patients should determine whether aberrant expression of plasma cell IL-1β is predictive of those MGUS patients that will eventually progress to active myeloma.

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Hyperdiploidy is less frequent in AL amyloidosis compared with monoclonal gammopathy of undetermined significance and inversely associated with translocation t(11;14)

Blood ◽

10.1182/blood-2010-02-268987 ◽

2011 ◽

Vol 117 (14) ◽

pp. 3809-3815 ◽

Cited By ~ 44

Author(s):

Tilmann Bochtler ◽

Ute Hegenbart ◽

Christiane Heiss ◽

Axel Benner ◽

Marion Moos ◽

...

Keyword(s):

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Monoclonal Gammopathy ◽

Early Stage ◽

Al Amyloidosis ◽

Tree Model ◽

Cytogenetic Aberrations ◽

Plasma Cell Disorders ◽

Undetermined Significance

Abstract In multiple myeloma (MM) pathogenesis, hyperdiploidy and nonhyperdiploidy are recognized as 2 major cytogenetic pathways. Here, we assessed the role of hyperdiploidy in 426 patients with monoclonal plasma cell disorders, among them 246 patients with AL amyloidosis (AL), by interphase fluorescence in situ hybridization. Hyperdiploidy was defined by a well-established score requiring trisomies for at least 2 of the 3 chromosomes 5, 9, and 15. The hyperdiploidy frequency in AL was a mere 11% compared with 30% in monoclonal gammopathy of undetermined significance (P < .001) and 46% in AL with concomitant MM I (P < .001). Overall, hyperdiploidy was associated with an intact immunoglobulin, κ light chain restriction, higher age, and bone marrow plasmacytosis, but was unrelated to the organ involvement pattern in AL. Clustering of 6 major cytogenetic aberrations in AL by an oncogenetic tree model showed that hyperdiploidy and t(11;14) were almost mutually exclusive, whereas gain of 1q21 favored hyperdiploidy. Deletion 13q14 and secondary IgH translocations were equally distributed between ploidy groups. We conclude that the interphase fluorescence in situ hybridization–based hyperdiploidy score is also a feasible tool to delineate hyperdiploid patients in early-stage monoclonal gammopathies and that the cytogenetic pathogenetic concepts developed in MM are transferable to AL.

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