Micromegakaryocytes (microMKs) are considered a myelodysplastic feature of myeloid neoplasms in adults, with an adverse prognosis connotation. However, this notion in MDS has not been well proved. In ...our cohort of 287 MDS, patients with microMKs showed lower overall survival (OS) (HR, 2.12; 95% CI, 1.47-3.06; p = 0.000036) and higher risk of acute myeloid leukemia (AML) evolution (HR, 4.8; 95% CI, 2.9-11.01; p = 0.00021). Results were validated with an independent cohort. In multivariate analysis, the presence of microMKs maintained its independent association with OS (HR, 1.54, 95% CI, 1.13-2.1, p = 0.0059) and AML transformation (HR, 2.28, 95% CI, 1.2-4.4, p = 0.014). Moreover, by adding 1 point to the IPSS-R score in patients with microMKs, we improved the IPSS-R accuracy. Interestingly, adding that 1-point, 29% of intermediate IPSS-R risk group patients were upgraded to the high-risk group. In summary, we confirmed that the presence of microMKs implies worse outcomes in MDS and suggested a modification improving IPSS-R.
Abstract
Objectives
New B-cell markers are needed for monitoring B lymphoblastic leukemia (B-ALL) in the era of immunotherapies directed against CD19 and CD22. The expression of leukocyte ...immunoglobulin-like receptor subfamily B member 1 (LILRB1) on hematogones in bone marrow (BM) and neoplastic B lymphoblasts has not yet been systematically investigated.
Methods
We assessed LILRB1 expression pattern on B cells in 19 control BMs and 22 B-ALL cases by flow cytometry.
Results
In all cases, mature B cells and hematogones exhibited a consistent pattern of LILRB1 expression with variable intensity over different stages of maturation, including a characteristic V-shaped pattern on hematogones. While neoplastic B lymphoblasts in all cases expressed LILRB1, the pattern of expression was distinctly abnormal relative to hematogones (loss of the dynamic pattern in all cases and abnormal expression levels in 83% of cases).
Conclusions
LILRB1 is a novel diagnostic B-cell marker to aid in distinguishing neoplastic B lymphoblasts from hematogones.
Introduction
The mechanism of relapsed CD19(−) B‐ALL after anti‐CD19 immunotherapy (Kymriah CART‐19 and blinatumomab) is under active investigation. Our study aims to assess LILRB1 as a novel B‐cell ...marker for detecting CD19(−) B‐lymphoblasts and to analyze the clinicopathologic/genetic features of such disease to provide biological insight into relapse.
Methods
Six patients (3 males/3 females, median age of 14 years) with relapsed CD19(−) B‐ALL were analyzed for cytogenetic/genetic profile and immunophenotype.
Results
CD19(−) B‐ALL emerged after an interval of 5.8 months following anti‐CD19 therapy. Five of six patients had B‐cell aplasia, indicative of a persistent effect of CART or blinatumomab at relapse. Importantly, LILRB1 was variably expressed on CD19(−) and CD19(+) B lymphoblasts, strong on CD34(+) lymphoblasts and dim/partial on CD34(−) lymphoblasts. Three of six patients with paired B‐ALL samples (pre‐ and post‐anti‐CD19 therapy) carried complex and different cytogenetic abnormalities, either as completely different or sharing a subset of cytogenetic abnormalities.
Conclusion
LILRB1 can be used as a novel B‐cell marker to identify CD19(−) B lymphoblasts. The emergence of CD19(−) B‐ALL appears to be associated with complex cytogenetic evolutions. The mechanism of CD19(−) B‐ALL relapse under anti‐CD19 immune pressure remains to be explored by comprehensive molecular studies.
Isolated trisomy 8 is not considered presumptive evidence of myelodysplastic syndrome (MDS) in cases without minimal morphological criteria. One reason given is that trisomy 8 (+8) can be found as a ...constitutional mosaicism (cT8M). We tried to clarify the incidence of cT8M in myeloid neoplasms, specifically in MDS, and the diagnostic value of isolated +8 in MDS. Twenty-two MDS and 10 other myeloid neoplasms carrying +8 were studied. Trisomy 8 was determined in peripheral blood by conventional cytogenetics (CC) and on granulocytes, CD3+ lymphocytes and oral mucosa cells by fluorescence in situ hybridization (FISH). In peripheral blood CC, +8 was seen in 4/32 patients. By FISH, only one patient with chronic myelomonocytic leukemia showed +8 in all cell samples and was interpreted as a cT8M. In our series +8 was acquired in all MDS. Probably, once discarded cT8M by FISH from CD3+ lymphocytes and non-hematological cells, +8 should be considered with enough evidence to MDS.
Summary
Trisomy 8 is the most common chromosomal gain in myelodysplastic syndromes (MDS), however, little is known about the features of MDS with isolated trisomy 8 and the influence of additional ...cytogenetic aberrations. We determined the characteristics and prognostic factors of 72 patients with trisomy 8 as a single anomaly and analysed also the impact of other aberrations added to trisomy 8 in another 62 patients. According to our study, MDS with isolated trisomy 8 was more frequent in men, with more than one cytopenia in most patients (62%) and having about 4% bone marrow blasts. The multivariate analysis demonstrated that platelet count and percentage bone marrow blasts had the strongest impact on overall survival (OS). The median OS for isolated trisomy 8, trisomy 8 plus one aberration (tr8 + 1), plus two (tr8 + 2) and plus three or more aberrations (tr8 + ≥3) was 34·3, 40, 23·4 and 5·8 months, respectively (P < 0·001). Trisomy 8 confers a poorer prognosis than a normal karyotype in MDS patients with ≥5% bone marrow blasts. This study supports the view that MDS with isolated trisomy 8 should be included in the intermediate cytogenetic risk group.
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