Frequent Expression of Cancer/Testis Antigens CT7 and LAGE-1 in Advanced Stage Multiple Myeloma: Are They Possible Targets for Immunotherapy?.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5034-5034
Author(s):  
Valeria Cristina da Costa Andrade ◽  
Gisele Wally Braga Colleoni ◽  
Andre L. Vettore ◽  
Roberta Spetic Felix ◽  
Manuella S.S. Almeida ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cell Line ◽  
High Frequency ◽  
Positive Control ◽  
Proliferation Index ◽  
Advanced Stage ◽  
Normal Bone Marrow ◽  
Normal Tissues ◽  
Normal Bone

Abstract Introduction: Recently, Jungbluth and collaborators (Blood2005;106(1):167) demonstrated that CT7 and MAGE-A3/6 are frequently expressed in advanced stage MM patients and that higher levels of CT7 and MAGE-A3/6 proteins also correlate with elevated plasma-cell proliferation index. These findings suggest a possible pathogenic role of such proteins in MM and also show that they could be attractive targets for immunotherapy. Objectives: To analyze global expression of 13 CTs (MAGE-A1, MAGE-A2, MAGE-A3/6, MAGE-A4, MAGE-A10, MAGE-A12, BAGE-1, CT7, GAGE family, LAGE-1, PRAME, SP17 and SSX-1) in a panel of normal tissues and monoclonal gammopathies. Material and Method: We studied 13 normal tissues (skeletal muscle, bladder, lung, spleen, heart, brain, thymus, uterus, stomach, mammary gland, pancreas, prostate and colon, Clontech), six normal bone marrow aspirates (donors for allogeneic stem-cell transplants), one pool of 10 normal bone marrow samples (Clontech), three monoclonal gammophaties of undertermined significance (MGUS), five solitary plasmacytomas, 39 multiple myeloma samples (two Durie-Salmon stage II and 37 stage III) and MM cell line U266. Normal testis was used as positive control. Total RNA was extracted using Trizol reagent (Invitrogen). After cDNA synthesis, the expression of CTs was evaluated by RT-PCR and 2% agarose gel electrophoresis. Results: SP17 was positive in all seven normal bone marrow samples and in the 13 normal tissues tested. Thus, it was excluded from further analyses. CT7 was positive in one MGUS and in one plasmacytoma. U266 cell line was positive for all CTs, except SSX-1. The frequency of CTs expression in MM patients was: CT7 = 30/39 (77%); LAGE-1 = 18/39 (46%); MAGE-A3/6 = 16/39 (41%); MAGE-A2 = 14/39 (36%); GAGE family = 13/39 (33%); BAGE-1 = 11/39 (28%); MAGE-A1 = 10/39 (26%); PRAME = 9/39 (23%); SSX-1 = 10/39 (26%); MAGE-A12 = 8/39 (20,5%); MAGE-A4 and MAGE-A10 = 0%. It is important to note that from the 18 cases with less CT’s positivity (0, 1 or 2 positive-CTs), three were negative for all of them. Twelve of the remaining 15 cases (80%) were positive for CT7. We did not find association between International Scoring System and percentage of expressed CTs in 36 analyzed MM cases. Conclusion: Our results showed high frequency of expression of CT7 in advanced stage MM patients and support its importance as a target for immunotherapy, because it has a high incidence of positivity even in cases without expression of other CTs. As far we know, this is the second study showing high frequency (~ 50%) of LAGE-1 expression in MM (van Baren et al, 1999), also highlighting its importance as therapeutic target.

Prognostication by miRNome-Profiling in Multiple Myeloma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1822-1822
Author(s):  
Anja Seckinger ◽  
Tobias Meißner ◽  
Vladimir Benes ◽  
Sabine Schmidt ◽  
Jonathan Blake ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cells ◽  
Proliferation Index ◽  
Normal Bone Marrow ◽  
Global Test ◽  
Myeloma Cells ◽  
Normal Bone ◽  
Bone Marrow Plasma

Abstract Abstract 1822 INTRODUCTION. MicroRNAs are an abundant class of small non-protein-coding RNAs that function as negative gene regulators in diverse biological processes including cancer by affecting the stability and translation of mRNAs. METHODS. We determined expression of 559 miRNAs by miChip (Exiqon LNA Array probes V9.2) in CD138-purified myeloma cells from previously untreated patients (n=69), normal bone marrow plasma cells of healthy donors (pooled to n=3), and human myeloma cell lines (n=20). For normalization, an invariant-based method was applied. Gene expression profiling was performed using Affymetrix U133 2.0 DNA-microarrays. RESULTS. We found 29 miRNAs to be significantly up- and 35 down-regulated in myeloma cells vs. normal bone marrow plasma cells, respectively. Expression of 18 miRNAs was simultaneously significantly (P<.01) associated with event-free survival (EFS) and overall survival (OS), and allowed the delineation of prognostic groups. Of these, miRNAs miR-659 (located at 22q12.1) was significantly lower expressed in myeloma cells compared to normal bone marrow plasma cells. For this miRNA, low expression delineates a group with inferior EFS (median 19.7 months vs. not reached, P<.001) and OS (median 52.9 months vs. not reached, P<.001). This group shows a significantly higher gene expression based proliferation index. In contrast, high miR-590 expression (located at 7q11.23) delineates a group with inferior EFS (median 12.4 vs. 36 months, P<0.001) and OS (median 29.4 months vs. not reached, P<.001). By using Goeman's global test, a significant association of the predicted target gene signatures with survival could be found for both, EFS (miR-590-5p, P<.001; miR-659, P<.001) and OS (P=.009; P=.002). CONCLUSION. In conclusion, we demonstrate the prognostic relevance of miRNome profiling in multiple myeloma. Disclosures: No relevant conflicts of interest to declare.

Microrna Expression Profiling in Acute Myelogenous Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1131-1131
Author(s):  
Fernando J. Suarez Saiz ◽  
Serban San-Marina ◽  
Mark D. Minden
Keyword(s):  
Bone Marrow ◽  
Cell Line ◽  
Cell Lines ◽  
Acute Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Erythroid Cell ◽  
Normal Bone Marrow ◽  
Hematopoietic Differentiation ◽  
Normal Bone ◽  
Acute Myelogenous

Abstract Acute myelogenous leukemia (AML) arises due to changes in gene expression that block or alter the normal differentiation program of hematopoietic stem cells. A variety of mutations in protein-encoding genes have been shown to contribute to the development of leukemia. Recently a new class of genes called microRNAs (miRNAs) have been identified. miRNAs are a subgroup of highly conserved, non-coding RNAs found only in eukaryotes. They do not encode proteins, and appear to have a significant effect on the proteome of a cell. Their conservation between species suggests their involvement in important biological functions, and in fact been shown to be involved in hematopoietic differentiation. While the function of most miRNAs is still unknown, it is believed that they regulate expression of target mRNAs by using the siRNA machinery either to promote degradation of the mRNA or to block its translation. To begin to understand the role of miRNAs in AML, we used Quantitative Polymerase Chain Reaction (QPCR) to measure the expression level of 20 miRNA precursors in the pro erythroid cell line K562, the pro-myelocytic cell line NB4, the myelomococytic cell line OCI/AML2, AML patients’ blasts and in normal bone marrow (NBM). The investigated miRNAs included some that are known to be specific for hematopoietic tissues or involved in hematopoietic differentiation, as well as all the miRNAs in chromosome 7, a hot spot for gene deletion in AML. Our findings indicate that miRNAs are differentially expressed in patients and cell lines when compared among themselves and against normal bone marrow. For example pre-miR-142 was expressed in NBM and K562 but was found to be elevated in OCI/AML2, NB4 and in all patient samples. Pre-miR-20 was found to be overexpressed in only a subset of patients. Other miRNAs like pre-miR-335 and pre-miR-148a were expressed in NBM and in some patients and not in the cell lines. In an effort to identify possible regulators of miRNA expression, we analyzed the upstream region of pre-miR-142 and found an LMO2 binding site. In AML, the LMO2 gene can be overexpressed relative to normal bone marrow and healthy lymphocytes. This transcription factor is involved in the regulation of genes important in the development of blood cells. To investigate if LMO2 could be involved in the regulation of miR-142 expression, we performed chromatin immunoprecipitation (ChIP) from K562 using an anti-LMO2 antibody. Only the LMO2 immunoprecipitation, and not those from the pre-immune control, were enriched in promoter DNA for pre-miR-142. This is consistent with the observation that miRNAs and coding RNAs can be regulated by the same environmental signals. Based on this observation we propose that oncogenes regulate in part the phenotype and biological behaviour of leukemia by affecting the expression of miRNAs. This further suggests that different forms of leukemia may be recognized based upon the spectrum of miRNAs they express.

Prognostic Impact of Cancer Testis Antigens Expression in Advanced Stage Multiple Myeloma Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4733-4733 ◽  
Author(s):  
Valéria C.C. Andrade ◽  
André L. Vettore ◽  
Manuella S.S. Almeida ◽  
José S.R. Oliveira ◽  
Maria de Lourdes L.F. Chauffaille ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Line ◽  
Prognostic Impact ◽  
Advanced Stage ◽  
Normal Tissues ◽  
Cancer Testis Antigens ◽  
Three Samples ◽  
Cox's Regression ◽  
Ct Antigens ◽  
Cancer Testis

Abstract Background: Cancer testis antigens have become the most extensively studied antigen group in the field of tumor immunology. Aims: This study aims to analyze global expression of 14 CT (cancer/testis) antigens in MM to identify possible prognostic markers and therapeutic targets. Patients and Methods: The expression of MAGEA1, MAGEA2, MAGEA3/6, MAGEA4, MAGEA10, MAGEA12, BAGE1, MAGEC1/CT7, GAGE family, LAGE-1, PRAME, NY-ESO-1, SPA17 and SSX1 was studied by RT-PCR in: 15 normal tissues, one pool of 10 normal bone marrow samples, three normal tonsils and bone marrow aspirates from six normal donors, three monoclonal gammophaties of undetermined significance (MGUS), five solitary plasmacytomas, 39 MM samples (95% advanced stage) and MM cell line U266. CodeLink Human UniSet I Bioarrays 10,000 genes was used for arrays analyses. Results: SPA17 was positive in all normal tissues and was excluded for further analyses. MAGEC1/CT7 was positive in bone marrow aspirates from one MGUS and in one plasmacytoma. U266 cell line was positive for all CT antigens, except SSX1. The frequencies of CT antigens expression in MM patients were: MAGEC1/CT7 = 30/39 (77%); LAGE-1 = 19/39 (49%); MAGEA3/6 = 16/39 (41%); MAGEA2 = 14/39 (36%); GAGE family = 13/39 (33%); NY-ESO-1 = 13/39 (33%); BAGE-1 = 12/39 (28%); MAGEA1 = 10/39 (26%); PRAME = 9/39 (23%); SSX-1 = 10/39 (26%); MAGEA12 = 8/39 (20.5%); MAGEA4 and MAGEA10 = 0%. Cox’s regression model showed that GAGE family positivity and number of positive CT antigens > 6 were independent prognostic factors when all patients were analyzed. However, MAGEC1/CT7 expression was the only independent prognostic factor when non-transplanted patients where analyzed. Three samples predominantly positive (> 6) and three samples predominantly negative (0 or 1) for the 13 analyzed CT antigens were submitted to microarrays analyses. 147 genes were overexpressed in predominantly positive CT antigens samples. Conclusions: Based on our findings, MAGEC1/CT7, MAGEA3/6 and LAGE-1 seem good candidates for immunotherapy, since together they are overexpressed in 85% of our MM cases. Besides, GAGE family expression, number of CT antigens > 6 and MAGEC1/CT7 seem to have impact on MM prognosis. Also, the results of arrays analyses corroborate the hypothesis that MM can be separate in two groups: predominantly positive and predominantly negative for CT antigens, meaning that these antigens may have important role for MM biology.

The Parthenolide Derivative LC-1 Is An Effective Single Agent and Is Highly Synergistic with Existing Therapies in Multiple Myeloma.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1708-1708
Author(s):  
Elisabeth J Walsby ◽  
Saman Hewamana ◽  
Alan Burnett ◽  
Steven Knapper ◽  
Chris Fegan ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cell Lines ◽  
Nuclear Localization ◽  
Plasma Cells ◽  
Bone Marrow Cells ◽  
Binding Capacity ◽  
Single Agent ◽  
Normal Bone Marrow ◽  
Normal Bone

Abstract Multiple myeloma (MM) remains incurable with conventional therapeutic agents and has a median survival of only 3–5 years. Therefore, there is clearly a need for novel treatment strategies that can change the natural pathology of this condition. The nuclear factor κB (NF-κB) family of transcription factors is constitutively activated in MM cell lines and the majority of MM patients. Since NF-κB has known oncogenic activity in a number of human malignancies, targeted inhibition of this family of proteins may be useful in the treatment of MM. We and others have recently shown that the parthenolide derivative LC-1 has activity in acute myeloid leukaemia (AML) and chronic lymphocytic leukaemia (CLL) cells. Unusually, it induces apoptosis via the activation of both the intrinsic and extrinsic pathways and apoptosis is preceded by marked inhibition of NF-κB. Importantly, LC-1 is more potent against primary AML blasts and CLL lymphocytes than normal bone marrow progenitors and normal B-cells and T-cells. In this study we set out to evaluate LC-1 in MM cell lines and plasma cells derived from MM patients. LC-1 was cytotoxic to MM cell lines H929, U266 and JJN3 and induced apoptosis in a dosedependent manner resulting in an overall LD50 of 3.6mM (±1.8) after 48 hours in culture. Primary myeloma plasma cells, identified by CD38 and CD138 positivity, had a mean LD50 for LC-1 of 5.4mM (±1.6) after 48 hours of in vitro culture. Normal bone marrow cells were significantly less sensitive to the effects of LC-1 under the same conditions (P = 0.0007). Treatment of MM cell lines with LC-1 resulted in a decrease in the nuclear localization of NF-κB, as evidenced by a dose-dependent decrease in the DNA binding capacity of the NF-κB subunit RelA after 4 hours of treatment. To demonstrate whether synergy exists between LC-1 and existing MM therapies, the H929 cell line was treated for 48 hours with LC-1 and doxorubicin (32:1), melphalan (1:1) or bortezimib (1:500) and the combination indices (CI) calculated using the median effect method. A combination index of less than 1 denotes synergy. LC-1 did not show synergy with doxorubicin (CI &gt;1) but was synergistic with melphalan and bortezimib (CI values of 0.53 and 0.59 respectively). Taken together our data clearly demonstrate that LC-1 has activity in MM cell lines and primary MM cells. Its ability to inhibit the nuclear localization of NF-κB is important to its cytotoxic effects. Furthermore, it may also provide an explanation for the synergy demonstrated with melphalan and bortezimib. These results provide a rationale for exploring the potential of LC-1 in clinical studies.

Frequency and Prognostic Relevance of Cancer Testis Antigen 45 Expression in Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5134-5134
Author(s):  
Valeria C.C. Andrade ◽  
Gisele W. B. Colleoni ◽  
Andre Luiz Vettore ◽  
Maria R. R. Silva ◽  
Roberta Spetic Felix ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cell Line ◽  
Plasma Cell ◽  
Cell Morphology ◽  
Staging System ◽  
Monoclonal Gammopathies ◽  
Normal Tissues ◽  
Cancer Testis

Abstract Introduction: Cancer testis (CT) antigens have become the most extensively studied antigen group in the field of tumor immunology. CT45 antigen expression was described in colon adenocarcinomas, germ cell tumors, Hodgkin’s lymphomas and, more recently, in multiple myeloma (MM). Aims: This study aims to analyze the expression of CT45 in normal tissues and in plasma cell disorders and to identify possible associations with clinical data and prognosis in MM. Patients and Methods: The expression of CT45 was studied in twenty normal tissues (testis, placenta, skeletal muscle, bladder, lung, spleen, heart, brain, fetal brain, thymus, uterus, stomach, mammary gland, pancreas, prostate, small intestine, kidney, adrenal gland, spinal cord, colon and one pool of ten normal bone marrow samples) and in bone marrow aspirates from three monoclonal gammopathies of undetermined significance (MGUS), five solitary plasmacytomas, 61 newly diagnosed MM patients and MM cell line U266 by RT-PCR. Results: CT45 was positive in three out of 20 (15%) normal tissues tested: lung, brain (both fetal and adult) and spinal cord. Among monoclonal gammopathies, CT45 was positive in two out of five (40%) solitary plasmacytomas’ bone marrow aspirates, 10 out of 61 (16%) MM bone marrow aspirates and in the U266 MM cell line. Six out of 10 (60%) CT45 positive MM cases were classified as International Staging System (ISS) 3 (p = 0.009). Six CT45-positive cases were classified as plasmacytic (PC) and four as polymorphic (PM). Median OS of the MM group was 21 months. Nine patients were submitted to autologous stem cell transplantation. All of the transplanted cases were CT45-negative. Univariate analysis showed that Durie-Salmon Staging System (Durie-Salmon IIIA: N = 35, median OS = 40 months; Durie-Salmon IIIB: N = 19, median OS = 12 months; log-rank p= 0.0139), b2microglobulin (b2microglobulin £ 5.5 mg/L: N = 27, median OS = 40 months; b2microglobulin &gt; 5.5 mg/L: N = 24, median OS = 12 months, log-rank p= 0.0520, Breslow p = 0.0352, Tarone-Ware p = 0.0399), plasma cell morphology (PC: N = 38, median OS = not reached; PM: N = 11, median OS = 12 months; PB: N = 5, median OS = 1 month; log-rank p= 0.0037), transplantation proceedings (transplanted patients: N = 9, median OS = not reached; non-transplanted patients: N = 47, median OS = 14 months; p = 0.0064) and CT45 expression (CT45 expression negative: N = 46, median OS = 25 months; CT45 expression positive: N = 10, median OS = 3 months, log-rank p = 0.038 for all patients and CT45 expression negative: N = 37, median OS = 19 months; CT45 expression positive: N = 10, median OS = 3 months, p = 0.0245, only non-transplanted patients) had impact on OS. Cox Regression Model showed that only plasma cell morphology (p = 0.029, RR 5.288, CI 1.77704–15.7988), transplant proceedings (p = 0.0742, RR 0.1582, CI 0.0209–1.1976) and CT45 expression (p = 0.0016, RR 7.0403, CI2.0978–23.6278) were independent prognostic factors in MM patients survival. CT45-positive cases were associated with poor outcome and presented 7 times more chance of worse evolution then the negative ones. Conclusions: CT45 was expressed in only 16% of MM patients. However, we demonstrated for the first time that positive expression of CT45 was associated with high ISS scores and poor outcome in MM

scholarly journals Role and Mechanism of circ_0058063/miR-635 Axis in the Malignant Phenotype of Multiple Myeloma RPMI8226 Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Xiaoya Li ◽  
Lingzhi Ding ◽  
Geyu Gu ◽  
Changjun Zheng ◽  
Chenshuai Pan ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Protein Expression ◽  
Migration And Invasion ◽  
Normal Bone Marrow ◽  
Malignant Phenotype ◽  
Ki 67 ◽  
Myeloma Cells ◽  
Bone Marrow Tissue ◽  
Normal Bone

Objective. This study aims to explore circ_0058063 effect on multiple myeloma cells malignant phenotype and its feasible mechanism. Methods. We selected 47 cases of multiple myeloma tissues and 47 cases of normal bone marrow tissues and then used RT-qPCR method to test circ_0058063 and miR-635 expression in the tissues. Myeloma cells RPMI8226 were transfected with si-circ_0058063, miR-635 mimic, and si-circ_0058063 + anti-miR-635, respectively. Then, we adopt CCK-8 method, flow cytometry method, and Transwell and western blot methods to detect the influences of knockdown of circ_0058063 or miR-635 overexpression on RPMI8226 cell proliferation, apoptosis, migration, and invasion and also Ki-67, Bax, Bcl-2, MMP-2, and MMP-9 protein expression. The dual luciferase reporter gene assay experiment proved that it has regulatory relationship between circ_0058063 and miR-635. Results. circ_0058063 expression of multiple myeloma was higher than that in normal bone marrow tissue ( P < 0.05 ), while miR-635 expression was lower than that in normal bone marrow tissue ( P < 0.05 ). Knockdown of circ_0058063 or overexpression of miR-635 could reduce proliferation capacity, migration, invasion cell quantities, and Ki-67, MMP-2, MMP-9, and Bcl-2 protein expression ( P < 0.05 ), while increasing apoptosis rate together with Bax protein expression ( P < 0.05 ). circ_0058063 targets to negatively regulate miR-635, while knocking down miR-635 reverses the influences of knocking down circ_0058063 on RPMI8226 proliferation, apoptosis, migration, and invasion. Conclusion. circ_0058063 expression increased in multiple myeloma tissues. Knocking down its expression may inhibit myeloma proliferation, migration, and invasion by targeting and upregulating miR-635 and also promote cell apoptosis. As for multiple myeloma treatment, circ_0058063/miR-635 may provide new molecular targets.

scholarly journals Deep Learning for Discovering and Identifying Morphological Heterogeneity of Neutrophils in Primary Hematological Diseases Based on Bone Marrow Neutrophils Analysis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 18-18
Author(s):  
Lintao Bi ◽  
Wen Gao ◽  
Lingjun Meng ◽  
Guiying Gu ◽  
Zhangzhen Shi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Deep Learning ◽  
Roc Curve ◽  
Learning Model ◽  
Normal Bone Marrow ◽  
Chronic Leukemia ◽  
Hematological Diseases ◽  
Normal Bone ◽  
Deep Learning Model

It has been known that neutrophils play an important role in regulating homeostasis and disease. Tumor-associated neutrophils (TANs), as an important member of the tumor microenvironment, have gradually been proved their roles in a variety of solid tumors. It is generally believed that the changes in blood cell morphology (including neutrophils) are the phenotype of hematological diseases (such as in myelodysplastic syndromes) or tumor cells themselves. However, whether there is a possibility that the accumulation of abnormal neutrophils function leads to the change of hematopoietic stem cells and this is just the reason of hematological diseases? Do neutrophils play a key role in the pathogenesis and development of hematological tumors, especially acquired or age-related blood diseases, such as most acute and chronic leukemia, multiple myeloma and other diseases? TAN also has polarization, which is similar to tumor-associated macrophages (TAM), suggesting that the function and morphology of neutrophils are closely associated. Therefore, we assumed that there are function-related morphological differences in neutrophils in different hematological diseases. Finding these differences may provide clues for the functional research of neutrophils in hematological diseases. Artificial intelligence represented by deep learning can distinguish images efficiently and accurately (such as face recognition). Here we try to apply deep learning to discovery and recognize the morphological difference among neutrophils in different hematological diseases. We obtained whole slide images (WSI) from 4 types of malignant hematological diseases, which is chronic myelogenous leukemia (CML), multiple myeloma (MM), acute myeloblastic leukemia with maturation (AML-M2), acute monocytic leukemia (AML-M5) and normal bone marrow. Neutrophils were segmented from WSI by two diagnostic physicians (one with more than 40 years of diagnostic experience and the other with 13 years of diagnostic experience) There are 6115 neutrophils, and the number of cells in each disease and normal bone marrow is 593, 1404, 2509, 850, and 759, respectively. We trained these neutrophils using the transfer learning algorithm and the ratio of training and verification groups is 80:20. We established a convolutional neural network (CNN) model based on the morphological phenotype of neutrophils to judge their disease classification and used confusion matrix and receiver operator characteristic (ROC) curve for model evaluation. We found that neutrophils from different diseases can be classified into different categories, and the deep learning model has a high accuracy rate for judging the neutrophils from different diseases. Moreover, according to the obtained mixed matrix results, it is found that some M2 and M5 neutrophils are prone to misjudgment, while M2 and M5 is rarely confused with other diseases. The reason for this may be that M2 and M5 are both acute myeloid leukemia. Neutrophils from MM and normal bone marrow are prone to misjudge each other or judged as CML neutrophils, and MM often involves the plasma cell system, so some neutrophils of MM may be similar to normal bone marrow. Compared with acute leukemia, some chronic leukemia neutrophils are close to MM or normal bone marrow. Based on these results, we can further confirm that there are morphological and phenotypic differences between different types of hematological diseases. According to the ROC curve results, it is suggested that the deep learning model constructed based on the feature extraction of the CNN model can more accurately determine different hematological diseases according to morphological phenotypes of neutrophils. These findings suggest that neutrophils in different hematological diseases have their own features. These features may provide more evidence for the diagnosis of the disease and also provide clues for further research on the function of TAN in primary hematological diseases. Disclosures No relevant conflicts of interest to declare.

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