Chromosomal Abnormalities in Bone Marrow Lymphocytes of MM Patients
Bibliographic record
Abstract
Abstract Abstract 4045 Multiple Myeloma (MM) is characterized by accumulations of chromosomal abnormalities throughout the course of disease. Recurrent IgH translocations such as t(4;14) or deletion (del)13 occur during early stages of disease or perhaps as originating events. Other abnormalities appear to be acquired late in the disease process, after development of frank MM, including p53 deletion (Ch17) and amplification of CKS-1B (Ch1). We have previously identified drug resistant clonotypic B lymphocytes in MM that have malignant characteristics and can xenograft MM to immunodeficient mice. Using an automatic scanning system we scanned bone marrow (BM) cytospin slides stained with May-Grünwald Giemsa to identify lymphocytes and to determine whether or not they share the same chromosomal abnormalities that are found in autologous plasma cells (PC). For 200 MM patients, we performed interphase FISH using commercial probes, to detect deletion of chromosome 13, any translocations in 14q32, t(4;14)(p16;q32),t(11;14)(q13;q32), deletion of p53 and a custom probe to detect amplification of CKS-1B. For patients harboring a given chromosomal abnormality in their PC, we found the identical abnormalities in BM lymphocytes for 35% of patients having del13, 30% having t(4;14) and 23% having t(11;14). Likewise we detected amplification of locus 4p16, 11q13, 14q32, trisomy 1 and trisomy 17 in 45%, 15%, 30%, 37.5% and 44% respectively in the lymphocytes of patients demonstrating those same abnormalities in the PC. In a more limited series of experiments using immuno-FISH, we observed that BM lymphocytes with chromosomal abnormalities expressed CD20. In contrast, amplification of CKS-1B or p53deletion were undetectable in lymphocytes from patients having these abnormalities in their PC. We are currently analyzing the impact of abnormalities present in BM lymphocytes with regards to the clinical parameters and survival. An update of these results will be given at the meeting. Given the compelling evidence that B cells comprise a clinically important compartment of the MM clone, this work suggests that fundamental genetic events shared by all compartments of the MM clone include recurrent IgH translocations and Ch13 deletions. However, further clonal expansion occurring during disease progression and after relapse may be restricted to the PC population, characterized by acquisition of p53 deletions and CSK1B amplification. Furthermore in overt MM, clonal expansion may simultaneously occur on at least two levels, firstly that of the B cells which persistently give rise to PC, and secondly that of PC themselves as they continue clonal expansion in the absence of contributions from the B cells. Abnormalities such as del13 or IgH translocations characterize early events in the disease while p53del or amplification of CKS-1B may occur as progression events restricted to PC. Disclosures: No relevant conflicts of interest to declare.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".