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

Blood ◽  
2011 ◽  
Vol 117 (14) ◽  
pp. 3809-3815 ◽  
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.

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

Blood ◽  
1995 ◽  
Vol 86 (10) ◽  
pp. 3915-3921 ◽  
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.

scholarly journals Frequent gain of chromosome band 1q21 in plasma-cell dyscrasias detected by fluorescence in situ hybridization: incidence increases from MGUS to relapsed myeloma and is related to prognosis and disease progression following tandem stem-cell transplantation

Blood ◽  
2006 ◽  
Vol 108 (5) ◽  
pp. 1724-1732 ◽  
Author(s):  
Ichiro Hanamura ◽  
James P. Stewart ◽  
Yongsheng Huang ◽  
Fenghuang Zhan ◽  
Madhumita Santra ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Disease Progression ◽  
Monoclonal Gammopathy ◽  
Poor Prognosis ◽  
Chromosome Band ◽  
Newly Diagnosed ◽  
Poor Prognostic Factor ◽  
Plasma Cell Dyscrasias

Using fluorescence in situ hybridization we investigated amplification of chromosome band 1q21 (Amp1q21) in more than 500 untreated patients with monoclonal gammopathy of undetermined significance (MGUS; n = 14), smoldering multiple myeloma (SMM; n = 31), and newly diagnosed MM (n = 479) as well as 45 with relapsed MM. The frequency of Amp1q21 was 0% in MGUS, 45% in SMM, 43% in newly diagnosed MM, and 72% in relapsed MM (newly diagnosed versus relapsed MM, P < .001). Amp1q21 was detected in 10 of 12 patients whose disease evolved to active MM compared with 4 of 19 who remained with SMM (P < .001). Patients with newly diagnosed MM with Amp1q21 had inferior 5-year event-free/overall survival compared with those lacking Amp1q21 (38%/52% versus 62%/78%, both P < .001). Thalidomide improved 5-year EFS in patients lacking Amp1q21 but not in those with Amp1q21 (P = .004). Multivariate analysis including other major predictors revealed that Amp1q21 was an independent poor prognostic factor. Relapsed patients who had Amp1q21 at relapse had inferior 5-year postrelapse survival compared with those lacking Amp1q21 at relapse (15% versus 53%, P = .027). The proportion of cells with Amp1q21 and the copy number of 1q21 tended to increase at relapse compared with diagnosis. Our data suggest that Amp1q21 is associated with both disease progression and poor prognosis.

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

Blood ◽  
1999 ◽  
Vol 93 (1) ◽  
pp. 300-305 ◽  
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

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.

Fluorescence In Situ Hybridization Studies in 22 Cases of Plasma Cell Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4461-4461
Author(s):  
Jianyong Li ◽  
Wei Xu ◽  
Lijuan Chen ◽  
Yu Zhu ◽  
Jinlan Pan ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Plasma Cell ◽  
Cell Leukemia ◽  
Molecular Cytogenetic ◽  
Cytogenetic Aberrations ◽  
Plasma Cell Disorder ◽  
Igh Rearrangement ◽  
Cell Disorder

Abstract Background Plasma cell leukemia (PCL) is a rare malignant plasma cell disorder that usually carries an aggressive course with a rapidly fatal outcome. Cytogenetic studies performed on plasma cell disorder are scarce and difficult because of the low proliferation rate of plasma cells. Fluorescence in situ hybridization (FISH) analysis is an attractive alternative for evaluation of numerical and structural chromosomal changes in PCL. Methods Interphase FISH (I-FISH) and two different specific probes for the regions containing 13q14.3 (D13S319) or 14q32 (IGHC/IGHV) were used to detect 13q14 deletion [del(13q14)] or IgH rearrangement in 22 PCL patients. For patients with IgH rearrangement, probes for IgH(JH) and 11q13 (CCND1) or 4p16 (FGFR3) were used to detect t(11;14)(q13;q32) or t(4;14)(p16;q32). Results Molecular cytogenetic aberrations were found in 19 of 22 (86.4%) PCL patients. Del(13q14) was detected in 13 cases (59.1%), and IgH rearrangement in 17 (77.3%) patients including 7 with t(11;14) and 3 with t(4;14). 14q32 rearrangement and 13q14 deletion were found concurrently in 11 cases (50%). Conclusions Chromosomal abnormalities are frequent in PCL. The most frequent aberrations among the cases was the 14q32 rearrangement and 13q14 deletion. I-FISH technique is useful to detect molecular cytogenetic aberrations and should be used in the routine evaluation of PCL.

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