BACKGROUND: CD34 is expressed by early hematopoietic (myeloid & lymphoid) progenitor cells, endothelial cells, and bone marrow stromal cells. Recent studies have suggested that the expression of the hematopoietic antigen CD34 is predictive of outcome. But the functional importance of CD34 antigen has not yet been fully elucidated, and CD34 antigen has not yet been included in the routine immunophenotyping panel. We designed this experiment to evaluate the significance of including CD34 antigen in the routine immunophenotyping panel. MATERIALS AND METHODS: We have included CD34 antigen in the immunophenotyping panel from 1994 to 1997. Seventy eight patients with acute leukemia and 7 patients with chronic leukemia and CML-blast crisis were analyzed by direct immunofluorescence using monoclonal antibodies. RESULTS: CD34 was positive in 64% (50/78) of cases with acute leukemia and 100% (3/3) of cases with CML-blast crisis, but negative in 100% (4/4) of cases with chronic lymphocytic leukemia. Seventeen (63%) of 27 patients that belonged to AML FAB subtype M0, M1, M2, M4, M5, M7 were CD34-positive, but all of the 9 patients (100%) that belonged to AML FAB M3 were CD34-negative. Thirty-one patients of CD34-positive non-T-ALL belonged to immunologic group II, III, or IV, and all 2 patients of CD34-positive T-ALL belonged to immunologic group I. There are no significant correlations of CD34 with the remission rate and the survival rate of acute leukemia. CONCLUSIONS: CD34 facilitates the rapid diagnosis of acute promyelocytic leukemia (APL) different from the other AML subtypes in clinical course and therapeutic plan. It is also helpful for the immunologic grouping of ALL, and differentiation of chronic leukemia from CML-blast crisis or acute leukemia. We concluded that it is desirable to include CD34 in the routine immunophenotyping panel.
Antibodies, Monoclonal ; Antigens, CD34 ; Diagnosis ; Endothelial Cells ; Fluorescent Antibody Technique, Direct ; Humans ; Immunophenotyping* ; Leukemia* ; Leukemia, Lymphocytic, Chronic, B-Cell ; Leukemia, Promyelocytic, Acute ; Mesenchymal Stromal Cells ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Stem Cells ; Survival Rate

Basic Helix-Loop-Helix Transcription Factors ; metabolism ; Chromosome Aberrations ; DNA Nucleotidylexotransferase ; metabolism ; Humans ; Immunoglobulin Light Chains ; metabolism ; Immunoglobulin Light Chains, Surrogate ; Lymphoma, B-Cell ; genetics ; metabolism ; pathology ; Lymphoma, T-Cell ; genetics ; metabolism ; pathology ; Membrane Glycoproteins ; metabolism ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; metabolism ; pathology ; Proto-Oncogene Proteins ; metabolism ; T-Cell Acute Lymphocytic Leukemia Protein 1

This study on determination of leukemia-specific chromosomal abnormalities and their relationship with prognosis of childhood acute leukemia (AL) had an important significance for childhood acute leukemia. In recent years, the efficacy of treatment of childhood AL has been greatly improved, but relapse is still a main factor affecting prognosis. Treatment based on the risk stratification by cytogenetic abnormalities can improve the prognosis and survival rate. In the past 3 decades, the genetic techniques have developed rapidly and many new genetic abnormalities have been found. This review highlights the main chromosomal and genomic abnormalities of 3 common childhood AL, including B-cell precursor acute lymphoblastic leukemia (BCP-ALL), T-cell acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML).
Acute Disease ; Child ; Humans ; Leukemia ; genetics ; Leukemia, Myeloid, Acute ; genetics ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; genetics

<b>OBJECTIVEb>To investigate the expression of CD123 and its significance in lymphocytic leukemia.

<b>METHODSb>CD123 expression in 139 lymphocytic leukemia patients and in lymphocytes from 10 normal bone marrows (BM) was analyzed by multi-parameter flow cytometry. Cytogenetic and minimal residual disease (MRD) analysis were performed in acute B-lymphocytic leukemia (B-ALL) patients.

<b>RESULTSb>CD123 expression was absent in B lymphoid lineage stem-progenitor cells, mature B and T lymphocytes from 10 normal BM. Among 139 lymphocytic leukemia patients, CD123 was negative in 5 T-ALL and 23 B-CLL patients. However, among 111 B-ALL patients, CD123 was expressed in 106 (12 pro B-ALL, 57 common B-ALL and 37 Pre B-ALL) (95.49%) but not in 5 mature B-ALL patients. There was a positive correlation between CD123 and p-Akt expression, and CD123 expression was much higher in hyperdiploid than in non-hyperdiploid B-ALL patients. A statistically significant difference in relapse rate within 12 months (MRD positive group: 63.04% vs MRD negative group 21.56%)and in disease free survival (DFS) time was found beween patients with MRD\[(36.06 +/- 2.62)%\] or not \[(48.23 +/- 1.82)%\] (P < 0.01). Moreover, stable CD123 expression could be observed in B-ALL patients in relapse.

<b>CONCLUSIONSb>CD123 was predominantly expressed in B-ALL patients and remained in patients in relapsec, indicating that it may be an useful MRD marker in B-ALL patients.

OBJECTIVE: To analyze the gene mutation profile in children with acute lymphocyte leukemia (ALL) and to explore its prognostic significance. METHODS: Clinical data of 249 primary pediatric ALL patients diagnosed and treated in the Department of Hematological Oncology of Wuhan Children's Hospital from January 2018 to December 2021 were analyzed retrospectively. Next-generation sequencing (NGS) was used to obtain gene mutation data and analyze the correlation between it and the prognosis of children with ALL. RESULTS: 227 (91.2%) were B-ALL, 22 (8.8%) were T-ALL among the 249 cases, and 178 (71.5%) were found to have gene mutations, of which 85 (34.1%) had ≥3 gene mutations. NRAS(23.7%), KRAS (22.9%),FLT3(11.2%), PTPN11(8.8%), CREBBP (7.2%), NOTCH1(6.4%) were the most frequently mutated genes, the mutations of KRAS, FLT3, PTPN11, CREBBP were mainly found in B-ALL, the mutations of NOTCH1 and FBXW7 were mainly found in T-ALL. The gene mutation incidence of T-ALL was significantly higher than that of B-ALL (χ²= 5.573，P＜0.05) and were more likely to have co-mutations (P＜0.05). The predicted 4-year EFS rate (47.9% vs 88.5%, P＜0.001) and OS rate (53.8% vs 94.1%, P＜0.001) in children with tp53 mutations were significantly lower than those of patients without tp53 mutations. Patients with NOTCH1 mutations had higher initial white blood cell count （128.64×10⁹/L vs 8.23×10⁹/L，P＜0.001）, and children with NOTCH1 mutations had a lower 4-year EFS rate than those of without mutations (71.5% vs 87.2%, P＝0.037). CONCLUSION Genetic mutations are prevalent in childhood ALL and mutations in tp53 and NOTCH1 are strong predictors of adverse outcomes in childhood ALL, with NGS contributing to the discovery of genetic mutations and timely adjustment of treatment regimens.
Child ; Humans ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Cell Cycle Proteins/genetics* ; Proto-Oncogene Proteins p21(ras)/genetics* ; Retrospective Studies ; Ubiquitin-Protein Ligases/genetics* ; Prognosis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; Mutation ; Lymphocytes

BACKGROUND: Aberrant myeloid antigen (MA) co-expression and high expression of CD34 antigen on the blasts of acute lymphoblastic leukemia (ALL) patients are independently reported to have a role in pathogenesis and prognosis. This study was conducted to determine whether these two parameters are related. METHODS: A total of 204 cases of ALL were included in an analysis of blast immunophenotypic data. CD34 expression was categorized as low when less than 50% of blasts were CD34-positive (CD34low) and as high when 50% or more were CD34-positive (CD34high). RESULTS: Of 204 cases of ALL, 163 and 41 were of B-cell origin (B-ALL) and T-cell origin (T-ALL), respectively. Of all cases, 132 (64.7%) showed co-expression of MA and among these, 101 (76.51%) were CD34high, while the remaining 31 (23.48%) were CD34low. Of 72 cases without MA co-expression, 25 (34.72%) were CD34high and 47 (67.25%) were CD34low. Furthermore, of 163 cases of B-ALL, 111 showed co-expression of MA and 84 of these were CD34high. Of 52 cases of B-ALL without MA expression, 22 were CD34high. Among 41 cases of T-ALL, 21 co-expressed MA, 17 of which were CD34high. Moreover, all 20 cases of T-ALL without co-expression of MA were CD34low. These differences were statistically significant. CONCLUSION: We observed a strong correlation between aberrant MA expression and CD34high expression on the blasts of ALL. We hypothesize that these different patient subsets may represent unique prognostic characteristics.
Antigens, CD34 ; B-Lymphocytes ; Flow Cytometry ; Humans ; Immunophenotyping ; Precursor Cell Lymphoblastic Leukemia-Lymphoma* ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; T-Lymphocytes ; Tertiary Care Centers*

Hemophagocytic lymphohistiocytosis (HLH), although uncommon, is illustrated as a dramatic clinical presentation of multi-systemic inflammation due to the impaired activity of cytotoxic T-cell and NK cell. Etoposide, an important component of the HLH treatment, is thought to have a leukemogenic potential. Furthermore, it has been suggested that the underlying immunologic dysfunction in HLH might be involved in the occurrence of secondary leukemia. Only a few cases of secondary ALLs after HLH have been reported. We report herein a case of secondary precursor B-cell ALL which occurred after the treatment of HLH.
Etoposide ; Inflammation ; Killer Cells, Natural ; Leukemia ; Lymphohistiocytosis, Hemophagocytic ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Precursor Cells, B-Lymphoid ; T-Lymphocytes

BACKGROUND: Precursor T-cell acute lymphoblastic leukemia (T-ALL) has worse prognosis than B-cell ALL. We aimed to evaluate prognostic variables in pediatric T-ALL. METHODS: Medical records of 36 T-ALL patients (27 males and 9 females; median age at diagnosis, 10.6 years) diagnosed and treated at Asan Medical Center from 2001 to 2017 were reviewed. Six patients (16.7%) had early T-cell precursor ALL (ETP-ALL). Most patients received the Children's Cancer Group-1882 (CCG1882) or Korean multicenter high risk ALL (ALL0601) protocols and prophylactic cranial irradiation. Clinical features at presentation, response to therapy, and treatment outcomes were analyzed. RESULTS: The six patients with ETP-ALL and 17 of 30 with non-ETP-ALL received CCG1882 or ALL0601 chemotherapy. Three patients, including two with ETP-ALL, did not achieve complete remission after induction. Rapid early response during induction was achieved by 26 patients. Five year overall survival (OS) and event free survival (EFS) rates were 71.4% and 70.2%, respectively. ETP-ALL and slow early response during induction were significant adverse prognostic factors, while hyperleukocytosis at diagnosis was not. CCG1882/ALL0601 chemotherapy resulted in superior survival (OS: 78.9%, EFS: 73.3%) compared with CCG1901 chemotherapy (OS: 64.3%, EFS: 64.3%), and patients undergoing prophylactic cranial irradiation had superior EFS to non-radiated patients. CONCLUSION: A high risk ALL protocol with intensified post-remission therapy, including prophylactic cranial irradiation, conferred T-ALL survival outcomes comparable with those of Western studies. Further treatment intensification should be considered for patients with ETP-ALL and slow induction responders. Additionally, CNS-directed treatment intensification, without prophylactic cranial irradiation, is needed.
B-Lymphocytes ; Chungcheongnam-do ; Cranial Irradiation ; Diagnosis ; Disease-Free Survival ; Drug Therapy ; Female ; Humans ; Male ; Medical Records ; Precursor Cell Lymphoblastic Leukemia-Lymphoma* ; Precursor Cells, T-Lymphoid ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; T-Lymphocytes*

OBJECTIVE: To investigate the changes of T lymphocyte subsets, B lymphocyte and NK cells in peripheral blood of patients with acute leukemia at different periods and their significance. METHODS: The peripheral T lymphocyte subsets and B lymphocyte of 95 patients with acute leukemia [(43 cases of acute lymphoblastic leukemia (ALL), 52 cases of acute myeloid leukemia (AML)] and 50 normal people were detected by flow cytometry respectively. RESULTS: The positive rate of CD3, CD3CD4, CD3CD8, NK cells and CD4/CD8 in the patients with newly diagnosed acute leukemia were significantly lower than those in normal controls (P<0.05) , but increased obviously after complete remission. The positive rate of Treg cells in the patients with newly diagnosed leukemia group was significantly higher than that in normal controls (P<0.01) , but decreased obviously after complete remission. Positive rate of CD3CD19 cells in the patients with newly diagnosed acute myeloid leukemia was significantly lower , but higher in the patients with newly diagnosed acute lymphoblastic leukemia than that in normal controls with statistical significant difference (P<0.05) , and increased obviously in the patients with acute myeloid leukemia (P<0.05) after complete remission , but decreased in the patients with acute lymphoblastic leukemia (P<0.01) after complete remission or no-remission. CONCLUSION Changes of T lymphocyte subsets, B lymphocytes and NK cells in the patients with newly diagnosed acute leukemia are significant, thus the detection of T lymphocyte cell subsets, B lymphocytes and NK cells can provide some evidences. for evaluation of the disease severity, curative efficiency and prognosis of patients with acute leukemia.
B-Lymphocytes ; Flow Cytometry ; Humans ; Killer Cells, Natural ; Leukemia, Myeloid, Acute ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; T-Lymphocyte Subsets

BACKGROUND: The CDK4I (cyclin dependent kinase 4 inhibitor) gene is on the chromosome 9p21. It encodes p16, which binds to CDK4, and inhibits phosphorylation of retinoblastoma protein (pRb) by D-type cyclin-CDK4 complex. D-type cyclin-CDK4 complex phosphorylates pRb which regulates transition of G1 to S phase of the cell cycle. So inactivation of the CDK4I gene leads to the dysregulation of the cell cycle and may contribute to the malignant progression of cells. Homozygous deletion of CDK4I gene was frequently found in human hematologic malignancies. The purpose of this study is to find the relationship between the CDK4I gene homozygous deletion and diverse acute leukemia. METHODS: We analyzed homozygous deletions of the CDK4I gene from 21 cases of acute leukemia by means of Southern blot analysis (10 B-cell acute lymphocytic leukemias, 6 T-cell acute lymphocytic leukemias, 5 acute myelogenous leukemias). Hybridization of EcoRI digested DNA using CDK4I probes (exon 1 and exon 2) obtained by PCR of human control DNA was performed. RESULTS: 1) We observed 4 cases (19%) of homozygous deletions in 21 cases of acute leukemia. 2) ALL 4 cases of homozygous CDK4I deletion were T-cell ALL which accounted for 66% (4/6 cases) of T-cell ALLs. 3) Homozygous CDK4I deletions were not found in any cases of B-ALLs (0/10 cases) and AML (0/5 cases). 4) In 4 cases of homozygous deletion, consistent results were obtained by 2 different CDK4I probes (pv 336-bp probe, pv 142-bp probe). CONCLUSION: The high frequency of CDK4I homozygous deletions in T-ALLs supports that the inactivation of these genes plays an important role in the pathogenesis of T- ALL.
B-Lymphocytes ; Blotting, Southern ; Cell Cycle ; DNA ; Exons ; Hematologic Neoplasms ; Humans ; Leukemia* ; Phosphorylation ; Phosphotransferases ; Polymerase Chain Reaction ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Retinoblastoma Protein ; S Phase ; T-Lymphocytes