OBJECTIVE: To explore the clinical characteristics and prognosis of children with SIL-TAL1-positive T-cell acute lymphoblastic leukemia ( SIL-TAL1⁺ T-ALL). METHODS: The clinical data of 110 children with newly diagnosed T-ALL admitted to the pediatric department of our hospital from January 2010 to December 2018 were reviewed to compare the clinical characteristics, treatment response and prognosis between SIL-TAL1⁺ group and SIL-TAL1^-group. RESULTS: Among the 110 children with T-ALL, 25 cases (22.7%) were in the SIL-TAL1⁺ group and 85 cases (77.3%) in the SIL-TAL1^- group. The white blood cell (WBC) count in the SIL-TAL1⁺ group was significantly higher than that in the SIL-TAL1^- group (P < 0.05), while the other clinical characteristics and treatment response were not significantly different between the two groups. The 5-year overall survival (OS) rates of SIL-TAL1⁺ group and SIL-TAL1^- group were 80.0% and 75.5%, and 5-year disease-free survival (DFS) rates were 76.0% and 72.9%, respectively. There were no significant differences in OS rate and DFS rate between the two groups ( P >0.05). In children aged < 10 years, the 5-year OS rate of SIL-TAL1⁺ group and SIL-TAL1^- group was 100% and 75.1%, respectively, and the difference between the two groups was statistically significant (P < 0.05). CONCLUSION Although the WBC level is significantly higher in children with SIL-TAL1⁺ T-ALL than that in those with SIL-TAL1^- T-ALL, the treatment efficacy is similar between the two groups. In children aged < 10 years, the longterm survival rate is superior in the SIL-TAL1⁺ group.
Humans ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis* ; Prognosis ; Child ; Male ; Female ; Survival Rate ; T-Cell Acute Lymphocytic Leukemia Protein 1 ; Child, Preschool ; Oncogene Proteins, Fusion ; Leukocyte Count

Objective: To assess the clinical characteristics and prognosis of patients with SIL-TAL1-positive T-cell acute lymphoblastic leukemia (T-ALL) . Methods: The clinical data of 19 SIL-TAL1-positive T-ALL patients admitted to the First Affiliated Hospital of Soochow University between January 2014 and February 2022 were retrospectively computed and contrasted with SIL-TAL1-negative T-ALL patients. Results: The median age of the 19 SIL-TAL1-positive T-ALL patients was 15 (7 to 41 years) , including 16 males (84.2%) . SIL-TAL1-positive T-ALL patients had younger age, higher WBC, and hemoglobin compared with SIL-TAL1-negative T-ALL patients. There was no discrepancy in gender distribution, PLT, chromosome abnormality distribution, immunophenotyping, and complete remission (CR) rate. The 3-year overall survival (OS) was 60.9% and 74.4%, respectively (HR=2.070, P=0.071) . The 3-year relapse-free survival (RFS) was 49.2% and 70.6%, respectively (HR=2.275, P=0.040) . The 3-year RFS rate of SIL-TAL1-positive T-ALL patients was considerably lower than SIL-TAL1-negative T-ALL patients. Conclusion: SIL-TAL1-positive T-ALL patients were connected to younger age, higher WBC, higher HGB, and poor outcome.
Adolescent ; Adult ; Humans ; Male ; Young Adult ; Chromosome Aberrations ; Oncogene Proteins, Fusion/genetics* ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Recurrence ; Retrospective Studies ; T-Cell Acute Lymphocytic Leukemia Protein 1/genetics* ; T-Lymphocytes ; Female ; Child

No abstract available.
Leukemia, Lymphocytic, Chronic, B-Cell* ; Leukemia, Myeloid, Acute*

OBJECTIVETo investigate the role of Tal1 gene, which is aberrantly expressed in 40%-60% of patients with T lymphocytic leukemia (T-ALL), in the proliferation of T-ALL cells.

METHODSWe established stable Jurkat-siTal1 and Jurkat-T1 cell lines by trasnfecting T-ALL Jurkat cells with lentiviral vectors to knock-down or overexpress Tal1. Jurkat cells transfected with negative control siRNAs for Tal1 knock-down (Jurkat-mock1) and over-expression(Jurkat-mock2) served as the control cells. The proliferation of the cells lines was assessed using CCK-8 assay, and the cell cycle distribution was determined by flow cytometry. The mRNA and protein expressions of cyclin-dependent kinase inhibitor 2 (CDKN2A) and cyclin-dependent kinase inhibitor 1 (CDKN2B) were measured by real-time RT-PCR and Western blotting, respectively.

RESULTSJurkat-T1 cells showed more active proliferation in vitro than Jurkat-mock2 cells, while Jurkat-siTal1 cells showed slower growth than Jurkat-mock1 cells. In Jurkat-T1 cells, G0/G1 phase cells were decreased and S phase cells increased compared with Jurkat-mock2 cells, and Jurkat-siTal1 cells showed increased G0/G1 phase cells and decreased S phase cells compared with Jurkat-mock1 cells. Real-time RT-PCR and Western blotting showed that Tal1 inhibited the cellular expression of CDKN2A and CDKN2B at both mRNA and protein levels.

CONCLUSIONTal1 promotes the growth and the transition from G0/G1 phase to S phase in T-ALL cells Jurkat by inhibiting the expressions of G0/G1 and S phase negative regulatory proteins CDKN2A and CDKN2B.

Apoptosis ; Basic Helix-Loop-Helix Transcription Factors ; metabolism ; Cell Cycle ; Cell Proliferation ; Cyclin-Dependent Kinase Inhibitor p15 ; metabolism ; Cyclin-Dependent Kinase Inhibitor p16 ; metabolism ; Humans ; Jurkat Cells ; Lentivirus ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; metabolism ; pathology ; Proto-Oncogene Proteins ; metabolism ; RNA, Small Interfering ; T-Cell Acute Lymphocytic Leukemia Protein 1

In order to improve the recognition of myeloid/natural killer cell acute leukemia and to reduce misdiagnosis, one case of myeloid/natural killer cell acute leukemia resembling acute promyelocytic leukemia(APL) was reported and the related articles published were reviewed. A series of clinical tests, the morphologic and immunophenotypic analysis of leukemia cells, cytogenetic and molecular biological examinations were performed. The results indicated that the patient had anemia, thrombocytopenia and leucocytosis, but no evidence of lymphadenopathy and hepatosplenomegaly. The morphology of leukemia cells was similar to that of abnormal promyelocytic cells, especially the variant of M3 (M3v) leukemia cells. The leukemia cells expressed CD117, CD33, CD15, CD56 and cMPO, but did not express CD34, HLA-DR, CD13 and CD16. Abnormal cytogenetics with del (7) (q22q32) was found. Neither t(15;17) nor PML/RARα gene rearrangement was detected. The patient failed to show a differentiation-induction response to all-trans retinoic acid(ATRA). In conclusion, the myeloid/natural killer cell leukemia is extremely rare. It is very important to distinguish the disorder from APL/M3v. The patient with myeloid/natural kill cell acute leukemia should be treated with chemotherapy as acute myeloid leukemia.
Aged, 80 and over ; Female ; Humans ; Leukemia, Large Granular Lymphocytic ; diagnosis ; Leukemia, Promyelocytic, Acute ; diagnosis ; etiology

This study was aimed to identify the characteristics of childhood myeloid/natural killer cell precursor acute leukemia (M/NKPAL), and to summarize the therapeutical experiences of this rare hematologic malignancy. A child case of M/NKPAL accompanied by CNS leukemia was enrolled in this study, the therapeutic regiments and the results of long time following up were analysed and evaluated. The results showed that the unusual child case of M/NKPAL with CNS infiltration was diagnosed, showing immunophenotype of CD7(+), CD33(+), CD34(+), CD56(+), HLA-DR(+), MPO(-) and negative for other NK cell, T and B cell differentiation antigens; the chromosomal abnormalities were trisomy 8 and deletion of chromosome 12p. The child case was treated with daunorubicin and cytarabine, and achieved complete remission. Then, 5 courses of acute myeloid leukemia-oriented chemotherapy were given as consolidation chemotherapy, all of the 5 courses contained high dose cytarabine. This child case was given 9 times of lumbar puncture and intrathecal injection, besides these, this case was also given cranial radiotherapy with a dose of 36 Gy. After treated with these methods, the child case achieved long-term complete remission. It is concluded that the M/NKPAL is a rare disease with distinctive immunophenotypic characteristics, acute myeloid leukemia-oriented chemotherapy regimen with high dose of cytarabine may be able to induce long-term remission.
Central Nervous System Neoplasms ; therapy ; Child, Preschool ; Consolidation Chemotherapy ; Female ; Humans ; Immunophenotyping ; Karyotyping ; Leukemia, Large Granular Lymphocytic ; therapy ; Leukemia, Myeloid, Acute ; therapy ; Treatment Outcome

This study was aimed to investigate the expression level of CIAPIN1 mRNA in leukemia patients and explore its significance in leukemias. The fresh bone marrow was collected from 112 newly diagnosed leukemia patients, the total RNA was extracted by means of TRIzoL, the cDNA was synthesized, the expression of CIAPIN1 mRNA was detected by real-time quantitative PCR using β-actin as internal reference; 10 normal healthy persons were selected as controls. The results showed that the expression of CIAPIN1 mRNA was statistically higher in acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) and chronic phase chronic myeloid leukemia (CML) patients than that in normal persons (p < 0.05); but there was no statistical difference between chronic lymphocytic leukemia (CLL) and normal persons (p > 0.05). It is concluded that the CIAPIN1 gene higher expresses in MNC of newly diagnosed leukemia patients, up-regulation of CIAPIN1 expression may play an important role in pathogenesis of leukemia.
Adult ; Bone Marrow Cells ; metabolism ; Case-Control Studies ; Female ; Gene Expression Regulation, Leukemic ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; Leukemia ; genetics ; metabolism ; pathology ; Leukemia, Lymphocytic, Chronic, B-Cell ; genetics ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; Leukemia, Myeloid, Acute ; genetics ; Male ; Middle Aged ; Young Adult

The study was purposed to investigate the expression of CD73 on bone marrow nucleated cells (BMMNC) in various leukemia subtypes and its relationship with cell differentiation of leukemia. Immunocytochemistry staining and Wright-Giemsa staining of BMMNC from 75 cases of leukemia, 11 cases of myelodysplastic syndrome (MDS), 13 cases of non-leukemic patients and 9 healthy adults were performed, and the CD73(+) ratio in BMMNC and its relationship with differentiation of leukemia cells were analyzed. The results showed that the ratios of CD73(+) in BMMNC of com-B ALL, pre-B ALL and PLL were significantly higher than those in B-CLL (p < 0.05). CD73(+) ratios in AML subtypes of M(1), M(2a), t (8; 21), t (15; 17), M(4) and M(5) were markedly higher than those in MDS respectively, but in M(6) and MDS were lower and had no statistical difference between them. CD73(+) ratios in T-ALL, B-CLL, M(6), MDS, non-leukemia patients and healthy adults were close to each other and all of them were lower than those in B-ALL and other AML subtypes. It is concluded that the expression of CD73 is associated with leukemia subtype, differentiation and development. The higher differentiation of leukemia cells, the lower of CD73 expression in myeloid and B lymphoid leukemia, but T-ALL does not meet this pattern.
5'-Nucleotidase ; metabolism ; Adolescent ; Adult ; Cell Differentiation ; Humans ; Leukemia ; metabolism ; pathology ; Leukemia, Lymphocytic, Chronic, B-Cell ; metabolism ; Leukemia, Myeloid, Acute ; metabolism ; Myelodysplastic Syndromes ; metabolism ; Young Adult

The aim of this study was to investigate the nucleotide sequence of one distinct fusion transcript of sil-tal1 in childhood T-ALL. The PCR product was cloned into plasmid vector and then sequenced. Genomic DNA was analyzed with PCR using the designed primer pairs representing distinct sequences. The product was sequenced and analyzed with database. The results indicated that 4 different fusion transcripts were detected at cDNA level, in which a part of exons or introns of sil are reserved respectively, and some additions and deletions existed. After analyzing genomic DNA sequence of leukemic cells, the breakpoint in gene sil of this case was proved to be different at DNA level from references. Hence, the sil-tal1 rearrangement was defined to be a new type. It is concluded tal1 rearrangement of leukemic cells in this case is a new type, which expresses classical and at least 3 variant fusion transcripts, presumably caused by extraordinary mechanisms of splicing and transcription in leukemic stem cells.
Base Sequence ; Basic Helix-Loop-Helix Transcription Factors ; genetics ; Child ; DNA Breaks ; DNA, Neoplasm ; genetics ; Humans ; Leukemia-Lymphoma, Adult T-Cell ; genetics ; Male ; Oncogene Proteins, Fusion ; genetics ; Proto-Oncogene Proteins ; genetics ; T-Cell Acute Lymphocytic Leukemia Protein 1 ; Transcription Factors

OBJECTIVETo characterize the time course of spontaneous differentiation of in vitro cultured human embryonic stem cells (hESCs) into hematopoietic cells to provide experimental evidence for induction of hematopoietic commitment of hESCs.

METHODSIn human embryoid bodies (hEBs) derived from spontaneous differentiation of chESC3, a hESC cell line we established previously, the expressions of such genes as KDR, Bmi1, Scl and gata2 were detected by RT-PCR every other day during the 12-day differentiation to monitor the process of the hematopoiesis. The hematopoietic stem cell marker CD34 was examined using flow cytometry to evaluate the efficiency of hematopoietic differentiation of the cells on days 6, 8, 10 and 12. The spontaneously differentiated hESCs were seeded in the hematopoietic colony culture system to study the hematopoietic colony forming ability. Immunocytochemical staining for CD45 was performed on the hEBs to examine the emergence of mature hematopoietic cells.

RESULTSThe expressions of the hematopoietic stem cell-related genes KDR and Bmi-1 were detected in the hESCs, and on days 4 to 6, the two genes were upregulated with prolonged cuture of the hEBs. Scl and gata2 gene expressions were detected since 6-8 days of culture and maintained high expressions till day 12. Flow cytometry revealed a gradual increase in CD34-positive cells in the culture, with positivity rates on days 6, 8, 10, and 12 of (1.4-/+0.4)%, (3.4-/+1.3)%, (5.5-/+2.2)%, and (5.1-/+1.7)%, respectively. The numbers of CD43-positive cell colonies on days 6, 8, 10, and 12 were 0, 7-/+2, 37-/+11, and 89-/+29 in each 10(5) cells, respectively. Immunocytochemical staining identified CD45-positive cells on days 10, 12, 15, and 18 in the cell colonies, with the positive cell numbers of 0, 40.5-/+15.09, 178.6-/+55.89, and 253.0-/+52.04, respectively.

CONCLUSIONThe hESCs undergo spontaneous hematopoietic differentiation in 3 stages, including the differentiation into germ layer-specific cells (days 6-8), expansion period of the hematopoitic progenitors (days 8-12), and maturation of the hematopoietic cells (after day 15).

Animals ; Antigens, CD34 ; metabolism ; Basic Helix-Loop-Helix Transcription Factors ; genetics ; Cell Culture Techniques ; Cell Differentiation ; Embryonic Stem Cells ; cytology ; metabolism ; GATA2 Transcription Factor ; genetics ; Gene Expression Regulation ; Hematopoietic Stem Cells ; cytology ; metabolism ; Humans ; Mice ; Nuclear Proteins ; genetics ; Polycomb Repressive Complex 1 ; Proto-Oncogene Proteins ; genetics ; Repressor Proteins ; genetics ; T-Cell Acute Lymphocytic Leukemia Protein 1 ; Time Factors