No abstract available.
Base Sequence ; Bone Marrow/pathology ; Child, Preschool ; Chromosomes, Human, Pair 12 ; Chromosomes, Human, Pair 17 ; Female ; Gene Rearrangement ; Humans ; Karyotype ; Oncogene Proteins, Fusion/genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/*diagnosis/genetics ; Sequence Analysis, DNA ; TATA-Binding Protein Associated Factors/*genetics ; Trans-Activators/*genetics ; *Translocation, Genetic

OBJECTIVETo study the C-myc gene and protein in T lymphoblastic lymphoma/leukemia (T-LBL/ALL) and its relationship to prognosis.

METHODS60 cases of T-LBL/ALL with follow-up data were studied by using immunohistochemical EnVision method for CD1a, CD3, εCD3, CD7, CD10, CD34, CD43, CD45RO, CD99, TDT, CD20, CD23, MPO, Ki-67 and C-myc. 20 cases of reactive lymph nodes were selected as normal control group of C-myc gene and protein. Fluorescence in-situ hybridization (FISH) for C-myc gene (located on chromosome8q24) was performed to detect its breakage and gain.

RESULTSAmong the 60 cases of T-LBL/ALL, immunohistochemistry results showed:the percentages of tumor cells expression of CD1a, CD3, εCD3, CD7, CD10, CD34, CD43, CD45RO, CD99 and TDT were 38.3% (23/60), 75.0% (45/60), 45.0% (27/60), 95.0% (57/60), 36.7% (22/60), 23.3% (14/60), 60.0% (36/60), 41.7% (25/60), 96.7% (58/60) and 93.3% (56/60). Separately, while CD20, CD23 and MPO were all negative. A figure of Ki-67 expression ≤ 80% was found in 36 cases and > 80% was found in 24 cases. The positive rate of C-myc protein was 66.7% (40/60) in 60 cases of T-LBL/ALL, was 0% (0/20) in 20 cases of reactivated lymphoid tissue (χ² = 26.67, P < 0.05). C-myc protein expression was positively correlated with the mediatinal width and Ki-67 index (P < 0.05). Fluorescence in-situ hybridization results showed that among the 60 cases of T-LBL/ALL, C-myc gene with breakage of 8q24 was detected in 6 cases (10.0%), and gains in 11 cases (18.3%). 20 cases of reactive lymph nodes were not occurred breakage and gains of C-myc gene. It is not significant between C-myc gene and protein expression (P > 0.05). In addition, in 60 cases of T-LBL/ALL, 12(20.0%) cases of C-myc protein and genetic abnormalities coexist. Log-rank analysis results: The prognosis of C-myc protein positive group was worse than negative group (P < 0.05). The relationship of C-myc gene and prognosis was not significant (P > 0.05). C-myc protein and genetic abnormality coexist is related with worse prognosis (P < 0.05). COX analysis results show that the C-myc protein positive group may be a independent poor prognosis factors (P < 0.05).

CONCLUSIONSC-myc may play an important role on the development of T-LBL/ALL. It may be a independent prognosis factors.

Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Leukocyte Common Antigens ; Lymph Nodes ; pathology ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; metabolism ; Prognosis ; Proto-Oncogene Proteins c-myc ; metabolism

No abstract available.
Adult ; Base Sequence ; Bone Marrow/pathology ; Chromosomes, Human, Pair 12 ; Chromosomes, Human, Pair 9 ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Molecular Sequence Data ; Oncogene Proteins, Fusion/*genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/*diagnosis/genetics/pathology ; Pregnancy ; Protein-Tyrosine Kinases/*genetics ; Sequence Analysis, DNA ; Translocation, Genetic

OBJECTIVETo estimate the significance of the adjustment of acute lymphoblastic leukemia (ALL) risk group by monitoring minimal residual disease(MRD).

METHODTotally 285 children ALL patients who were diagnosed and systematically treated according to CCLG-2008 in Institute of Hematology and Blood Diseases Hospital, CAMS and PUMC, from April 2008 to August 2011 were prospectively selected. Among these cases, 62.8% (n = 179) were boys and 37.2% (n = 106) were girls and the median age was 5.3(0.5-14.0). The patients who were at high-risk group initially were excluded. The grouping of cases: the patients were divided into two groups according to the dates of initial diagnosis. Group I had 126 patients who were initially diagnosed between April 2008 and December 2009 in whom therapeutic regimen was not adjusted by reassignment of risk group by MRD. Group II had 159 patients who were initially diagnosed between January 2010 and August 2011 whose therapeutic regimen was adjusted by reassignment of risk group by MRD at specific time (33rd day of induction chemotherapy and 12 weeks after the beginning of chemotherapy). MP-FCM Coulter FC-500 was used in the detection of MRD.

RESULTAmong these 285 patients, 94.0% (n = 268) were diagnosed as B-lineage acute lymphoblastic leukemia and 6.0% (n = 17) were T-lineage acute lymphoblastic leukemia. In group I, 61.9% (n = 78) patients belonged to low-risk group, 38.1% (n = 48) median-risk; in group II, before the adjustment, the rates of the low-risk group and median-risk group were 68.6% (n = 109) and 31.4% (n = 50) , respectively, while after the adjustment they were altered to 53.5% (n = 85) and 39.6% (n = 63) , furthermore 6.9% (n = 11) patients went into the high-risk group. Both groups were followed up for 2.5 years after their diagnoses, the disease of 7.4% (n = 21) patients relapsed, and the rates of two groups were 12.7% (n = 16) and 3.1% (n = 5) respectively, P = 0.009. The rate of serious infection (such as sepsis, pulmonary infection) of all these patients was 32.3% (92/285) , there was no significant difference between the two groups [28.6% (36/126) vs.35.2% (56/159) , P = 0.392]. The mortality of all these patients was 6.7% (19/285) , and that of group I was higher than that of group II [10.3% (13/126) vs. 3.8% (6/159) , P = 0.044]. The 2.5 years overall survival (OS), event-free survival (EFS) and disease-free survival (DFS) of group I were all lower than those of group II in Kaplan-Meier survivorship analysis (all P < 0.05). The two groups were followed up for 2.5 years after their diagnoses, after elimination of the confounding influence of sex, age, FAB subtype, WBC count, ratio of blast cells in bone marrow at diagnosed, chromosome karyotype and fusion gene, reassignment of risk group by MRD was used to calculate the OS, EFS and DFS of ALL patients (all P < 0.05). After the adjustment the risk group was more significant in the assessment of prognosis.

CONCLUSIONThe reassignment of risk group in low and median risk groups children with acute lymphoblastic leukemia by MRD did not increase the rate of serious infection but could reduce the relapse rate and mortality, and was beneficial to increase the patients' OS, EFS and DFS.

Adolescent ; Antineoplastic Agents ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Bone Marrow ; pathology ; Child ; Child, Preschool ; Disease-Free Survival ; Female ; Flow Cytometry ; Humans ; Infant ; Male ; Neoplasm, Residual ; diagnosis ; drug therapy ; pathology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; drug therapy ; pathology ; Prognosis ; Prospective Studies ; Recurrence ; Remission Induction ; Survival Rate ; Treatment Outcome

Transformation of MDS into ALL during childhood is extremely rare. We report a rare case of an 8-yr-old girl who presented with refractory cytopenia of childhood (RCC) that transformed into ALL only 3 months after the diagnosis of childhood MDS. Although no cytogenetic abnormalities were observed in conventional karyotype and FISH analysis, we found several deletions on chromosomes 5q, 12q, 13q, and 22q. Partial homozygous deletion of the RB1 gene was observed on microarray analysis, with the bone marrow specimen diagnosed as ALL. This is the first case report of transformation of ALL from childhood MDS in Korea. We also compared the clinical, cytological, and cytogenetic features of 4 previously reported childhood MDS cases that transformed into ALL.
Bone Marrow Cells/pathology ; *Cell Transformation, Neoplastic/genetics ; Child ; Chromosome Aberrations ; Female ; Gene Deletion ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Myelodysplastic Syndromes/*diagnosis/genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/*diagnosis/genetics ; Retinoblastoma Protein/genetics

This study was purposed to investigate the dynamically monitoring minimal residual disease (MRD) by flow cytometry (FCM) in patients with acute leukemia (AL) after complete remission and its relation with prognosis. From October 2010 to May 2012, 58 cases of AL (including 45 cases of AML and 13 cases of ALL) were regularly monitored for MRD in bone marrow by FCM and their bone marrow morphology was observed by light microscopy at the same time which continued to relapse or to follow-up deadline in the Department of Hematology, the First Affiliated Hospital of Zhengzhou University. Through average follow-up for 9 months (3 - 21 months), the average MRD level of patients with CR was got. And the prognostic value of MRD level at different time points in AL patients after CR was analysed and summarized. MRD ≥ 1% was defined as positive, otherwise, as negative. The results showed that the maximum and minimum MRD levels of 45 AML patients were 9.57% and 0.01% respectively, the average was 0.67%; the maximum and minimum MRD levels of 13 cases of ALL patients were 7.9% and 0.0016% respectively, the average was 0.99%. Among 44 cases after induction therapy, the relapse rate of MRD(+) group was 53.3% (8/15), the relapse rate of MRD(-) group was 10.3% (3/29), and the relapse rate of MRD(+) group was higher than that of MRD(-) group (χ(2) = 7.58, P = 0.006). Among 58 cases after the first consolidatory therapy, the relapse rate of MRD(+) group was 62.5% (5/8), the relapse rate of MRD(-) group was 16.0% (8/50), and the relapse rate of MRD(+) group was higher than that of MRD(-) group (χ(2) = 6.11, P = 0.013). It is concluded that MRD detected by FCM has a large range (10(-6) - 10(-2)), which can not be used as a single indicator of complete remission. When MRD ≥ 1% after induction therapy and the first consolidatory therapy, the relapse rate significantly increases, MRD can be used as a sensitive indicator for prognosis.
Adolescent ; Adult ; Aged ; Female ; Flow Cytometry ; Humans ; Leukemia, Myeloid, Acute ; diagnosis ; pathology ; Male ; Middle Aged ; Neoplasm, Residual ; diagnosis ; pathology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; pathology ; Prognosis ; Recurrence ; Remission Induction ; Young Adult

CD4 Antigens ; metabolism ; CD56 Antigen ; metabolism ; Dendritic Cells ; pathology ; Diagnosis, Differential ; Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor ; Hematologic Neoplasms ; drug therapy ; genetics ; metabolism ; pathology ; surgery ; Humans ; Immunohistochemistry ; Leukemia, Myeloid ; pathology ; Lymphoma, Extranodal NK-T-Cell ; pathology ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; pathology ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; pathology ; Skin Neoplasms ; drug therapy ; genetics ; metabolism ; pathology ; surgery

Central nervous system (CNS) is one of places in which direct infiltration and involvement or relapse occur in adult lymphocytic leukemia. The main mechanism of CNS infiltration in leukemia is associated with blood brain barrier (BBB), however the ALL CNS infiltration is difficulty early predicted and evaluated.For this reason, the studies on accurately evaluating the ALL CNS infiltration have important significance for early diagnosis and adjustment of therapeutic regimen, performance of individualised treatment and improvement of ALL patient's prognosis. In this article, the pathway of ALL CNS infiltration and its molecular mechanism, the evaluation methods for BBB function are reviewed.
Blood-Brain Barrier ; Central Nervous System Neoplasms ; diagnosis ; pathology ; Early Diagnosis ; Humans ; Neoplasm Invasiveness ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; pathology

This study was purposed to explore the application value of fluorescence in situ hybridization (FISH) detection in differential diagnosis of chronic myeloproliferative disorders (CMPD) and Ph(+) acute lymphoblastic leukemia (Ph(+) ALL), as well as in dynamic monitoring of minimal residual disease (MRD) after treatment. The BCR/ABL fusion gene of newly diagnosed and treated cases was detected by using BCR/ABL (ES) probe and BCR/ABL (DF) probe respectively. The results showed that among 49 newly diagnosed cases considered as CMPD, 28 cases met the criterion of CML morphologically, out of them 23 cases were eventually diagnosed to be CML and with morphological consistent rate 82.1% (23/28), the sensitivity and specificity all were 100% (23/23). The BCR/ABL positive rate of eventually diagnosed cases was 81.3% ± 17.7%. Among 13 cases received allogeneic haemopoietic stem cell transplantation (allo-HSCT), 9 cases achieved long-term disease-free survival and 4 cases relapsed, the several monitoring for whom after donor lymphocyte infusion (DLI) and imatinib treatment or allo-HSCT showed BCR/ABL negative. Among 16 cases treated with imatinib, 11 cases remained BCR/ABL negative after 1 year; 5 cases showed BCR/ABL positive during 6, 7 and 10 years after treatment, respectively, but out of them BCR/ABL positive in 1 case turned negative after allo-HSCT. It is concluded that the FISH is sensitive and specific diagnostic technique, the detection of BCR/ABL fusion gene in newly diagnosed and treated cases by using 2 different probes can help to fast and accurately determine the differential diagnosis for CML and Ph(+) ALL, and dynamically monitor the MRD after treatment with imatinib and allo-HSCT.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Diagnosis, Differential ; Female ; Fusion Proteins, bcr-abl ; genetics ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Middle Aged ; Myeloproliferative Disorders ; diagnosis ; pathology ; Neoplasm, Residual ; pathology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; pathology ; Retrospective Studies ; Sensitivity and Specificity ; Young Adult

Protein-losing enteropathy (PLE) is a syndrome characterized by excessive gastrointestinal protein loss, resulting in hypoproteinemia and edema. A variety of benign and malignant conditions can be associated with PLE and acute leukemia is a very rare cause of PLE. We report a case of PLE associated with acute lymphoblastic leukemia. A 27-year-old man was admitted due to watery diarrhea, epigastric pain and bilateral leg edema. Laboratory findings showed hypoproteinemia and polycythemia. The diagnosis of PLE and acute lymphoblastic leukemia were confirmed on the measurement of fecal alpha1-antitrypsin clearance and bone marrow examination. After systemic chemotherapy and autologous stem cell transplantation, his clinical symptoms and abnormal laboratory findings were gradually improved.
Adult ; Bone Marrow Cells/pathology ; Endoscopy, Gastrointestinal ; Humans ; Magnetic Resonance Imaging ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications/*diagnosis/genetics ; Protein-Losing Enteropathies/complications/*diagnosis ; Thoracic Vertebrae/radiography ; Tomography, X-Ray Computed ; Translocation, Genetic ; alpha 1-Antitrypsin/analysis