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

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

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

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

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

OBJECTIVETo screen childhood ALL related microRNAs (miRNAs), analyze association of miRNAs expression profiles with prognosis and relapse in childhood acute lymphoblastic leukemia (ALL) and explore new indicator for predicting relapse and prognosis.

METHODSmiRNAs expression profile was analyzed by gene chip in 49 newly diagnosed childhood ALL and 12 primary immune thrombocytopenia (ITP) cases (as control group). Abnormal expression of miRNAs was verified by qRT-PCR. The correlation of miRNAs expression pattern with indicators predicting early prednisone response and relapse within a year was analyzed.

RESULTSSpecific expression of miRNAs profiles associated with prednisone response and early relapse in childhood ALL was identified. Eight miRNAs (miR-18a, miR-532, miR-218, miR-625, miR-193a, miR-638, miR-550 and miR-633) could distinguish prednisone sensitive from insensitive. The early relapse of newly diagnosed patients with either high-risk or non-high-risk clinical types had some characteristics of abnormal expression of miRNAs, including miR-7, miR-216 and let-7i upregulated, while miR-486, miR-191, miR-150, miR-487 and miR-342 downregulated.

CONCLUSIONSThe initial screening reveals miRNAs differentially expressed from normal in ALL suggesting the potential roles of them in leukemogenesis. MiRNAs expression signatures may be useful for predicting prognosis and relapse in childhood ALL and directing personalized treatment.

Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; MicroRNAs ; genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; genetics ; pathology ; Prognosis ; Recurrence ; Transcriptome

OBJECTIVETo explore genes associated with risk classification of childhood acute lymphoblastic leukemia (ALL) by gene chip technology.

METHODSGroup A and B were both composed of three newly diagnosed ALL cases with standard risk. After re-evaluation, group B was relegated to high-risk. The control group was composed of three idiopathic thrombocytopenic purpura (ITP) patients. The gene expression profiles of group A and B were studied by Illumina Human-6 Beadchip. Eighty-two ALL patients were selected as the experimental group and 21 with normal bone marrow as control group for real-time quantitative RT-PCR (RQ-PCR).

RESULTS(1) There were 19 genes expressed differently between group B and A, including 14 up-regulated as ABCC4 and BCL11A, 5 down-regulated genes as TOP2A. (2) ABCC4 and BCL11A were validated by RQ-PCR and their expression level was higher in the high risk group than in the standard risk group (P < 0.05). The gene expression level in the group A and B was higher than that in the normal control group (P < 0.01). TOP2A was also validated by RQ-PCR and its expression level in the high risk group was lower than that in the standard risk group (P < 0.05). The gene expression level in the groups A and B was lower than that in the normal control group and the difference was statistically significance (P < 0.01). (3) There was a significant difference in the expression level of ABCC4 between the remission and unremission patients (P < 0.05). There was no significant difference in the expression level of BCL11A between different clinical indicators (P > 0.05). There was significant difference in the expression level of TOP2A between remission and prednisone good responder groups (P < 0.05).

CONCLUSIONSFourteen genes studied were involved in the pathogenesis and drug resistance mechanism in childhood ALL patients. Investigation of gene expression profile will be helpful for predicting drug resistance, prognosis, early intervention and target therapy in childhood ALL.

Child ; Drug Resistance, Neoplasm ; Female ; Gene Expression ; Gene Expression Profiling ; Humans ; Male ; Oligonucleotide Array Sequence Analysis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; genetics ; pathology ; Prognosis ; Risk Factors ; Transcriptome

In B lymphoblastic leukemia/lymphoma (B-ALL/LBL), t(9;22)(q34;q11.2) and t(1;19)(q23;p13.3) are recurrent cytogenetic abnormalities. The concurrent occurrence of both abnormalities is very rare, and only 3 cases have been previously reported. Here, we report a case of adult B-ALL with ider(9)(q10)t(9;22)(q34;q11.2) and der(19)t(1;19)(q23;p13.3). A literature review revealed that ider(9) (q10)t(9;22) is a rare variant of t(9;22) with a deletion of the short arm of chromosome 9. Fifteen cases of ider(9)(q10)t(9;22) have been reported. This abnormality is specific to precursor B-lymphoid neoplasms, such as B-ALL or B-lymphoid blast phase of CML, and is associated with disease progression or short survival. The cytogenetic abnormality t(1;19) is also specific to B-ALL. In most instances of t(1;19), TCF3 is fused to PBX1; however, a few cases have identical translocations but no TCF3-PBX1 fusion, as was observed in our patient. We describe the first case of ider(9)(q10)t(9;22) in combination with TCF3-PBX1 negative t(1;19). The patient underwent imatinib therapy in addition to intensive chemotherapy, but failed to achieve remission.
Bone Marrow Cells/cytology/pathology ; Chromosome Deletion ; Chromosomes, Human, Pair 1 ; Chromosomes, Human, Pair 19 ; Chromosomes, Human, Pair 22 ; Chromosomes, Human, Pair 9 ; Female ; Fusion Proteins, bcr-abl/genetics/metabolism ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Middle Aged ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/*diagnosis/genetics ; *Translocation, Genetic

The translocation t(10;11)(p13;q14q21) has been found to be recurrent in acute lymphoblastic and myeloid leukemias, and results in the fusion of the clathrin assembly lymphoid myeloid leukemia (CALM) gene with the AF10 gene; these genes are present on chromosomes 11 and 10, respectively. Because the CALM-AF10 rearrangement is a rare chromosomal abnormality, it is not included in routine molecular tests for acute leukemia. Here, we describe the cases of 2 patients with the CALM-AF10 fusion gene. The first patient (case 1) was diagnosed with T-cell ALL, and the second patient (case 2) was diagnosed with AML. Both patient samples showed expression of the homeobox A gene cluster and the histone methyltransferase hDOT1L, which suggests that they mediate leukemic transformation in CALM-AF10-positive and mixed-lineage leukemia-AF10-positive leukemias. Both patients achieved complete remission after induction chemotherapy. The first patient (case 1) relapsed after double-unit cord blood transplantation; there was no evidence of relapse in the second patient (case 2) after allogenic peripheral blood stem cell transplantation. Since CALM-AF10- positive leukemias have been shown to have poor prognosis with conventional therapy, molecular tests for CALM-AF10 rearrangement would be necessary to detect minimal residual disease during follow-up.
Adolescent ; Adult ; Bone Marrow/pathology ; Chromosomes, Human, Pair 10 ; Chromosomes, Human, Pair 11 ; Cord Blood Stem Cell Transplantation ; Female ; Histone-Lysine N-Methyltransferase/genetics/metabolism ; Homeodomain Proteins/genetics/metabolism ; Humans ; Leukemia, Myeloid, Acute/diagnosis/*genetics/therapy ; Male ; Monomeric Clathrin Assembly Proteins/*genetics ; Oncogene Proteins, Fusion/*genetics ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis/*genetics/therapy ; Recurrence ; Transcription Factors/*genetics ; Translocation, Genetic