CD34, CD56 and CD2 Are Predictive of NPM1 Mutation, FLT3-ITD and Their Favorable Prognosis Combination in Cytogenetically Normal Acute Myeloid Leukemia.
Bibliographic record
Abstract
Abstract Abstract 1576 Poster Board I-602 Introduction In cytogenetically normal acute myeloid leukemias (CN-AML), mutations of nucleophosmin (NPM1) gene and internal tandem deletion of Fms-related tyrosine kinase 3 (FLT3-ITD) are used to stratify them into prognostically distinct groups: CN-AML patients with mutated NPM1 (NPM1-mt) and wild type FLT3 (FLT3-wt) form a group with favorable prognosis, whereas those with wild type NPM1 (NPM1-wt) and FLT3-ITD make up the less favorable prognosis group. FLT3 mutations in tyrosine kinase domain (FLT3-TKD) are much less common and their prognostic significance is uncertain. Molecular testing for these abnormalities is expensive, time consuming and not widely available. Methods We have retrospectively correlated flow cytometric profile of patients with CN-AML with abnormalities of NPM1 and FLT3, in 79 unselected CN-AML patients between the ages of 19 and 60, and who also had blast cell DNA available for determination of FLT-3 and NPM1 mutation status. The FLT3-ITD was detected by DNA PCR and the NPM1 mutation and FLT-3 point mutation by direct sequencing of exons 12 and exon 20, respectively. The 4-color flow cytometry was performed using some or all of the following antibodies: HLA-DR, CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD11b, CD11c, CD13, CD14, CD15, CD19, CD20, CD22, CD33, CD34, CD45, CD56, CD61, CD64, CD71, CD79a, CD117, TDT, and MPO. All the plots were reviewed by two investigators (BD, MM) and listmode files reanalyzed as necessary. The antigen expression was recorded as negative/positive, dim/moderate/bright and partial/complete and correlated with NPM1-mt, FLT3-ITD and FLT3-TKD using 2×2 contingency tables and Fisher's exact test. Results 42 (53%), 34(43%) and 5 (6%) of 79 patients were NPM1-wt, FLT3-ITD and FLT3-TKD respectively. NPM-wt patients were more likely to be CD34+ (93%, p<0.0001, positive predictive value 89%, see figure); moreover, all patients with aberrant expression of CD2 (n=6) were NPM-wt (p=0.028). FLT3-ITD patients were more likely to be CD56+ (62%, p=0.02). 15/79 (19%) patients had unfavorable combination of NPM1-wt / FLT3-ITD, while 18 (23%) had favorable combination of NPM1-mt / FLT3-wt. The other two combinations NPM1-mt / FLT3-ITD and NPM1-wt / FLT3-wt had 19 (24%) and 27 (34%) patients respectively. Those with favorable combination were more likely to be CD56- (93%, p=0.0062, see figure), than all others. The patients with FLT3-TKD tended to be CD19+ (3/5) compared to those without TKD (15/71); however, due to low frequency of this mutation, the data is not statistically significant (p=0.0831). The remaining antigens, the intensity of staining and duality of populations (only a subpopulation positive) did not correlate NPM1 or FLT3 gene aberrations, nor with any of their combinations. Conclusions In CN-AML patients, flow cytometric demonstration of CD2+ and CD34- can predict NPM1-mt, while CD56+ can predict FLT3-ITD. CD56 can also identify the patients with favorable combination of NPM1-mt/FLT3-wt. 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) | 0.002 | 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".