Ultraconserved long non-coding RNA uc 112 is highly expressed in childhood T versus B-cell acute lymphoblastic leukemia

ABSTRACT Aberrant expression of long non-coding RNAs (lncRNAs) has been detected in several types of cancer, including acute lymphoblastic leukemia (ALL), but lncRNA mapped on transcribed ultraconserved regions (T-UCRs) are little explored. The T-UCRs uc.112, uc.122, uc.160 and uc.262 were evaluated by quantitative real-time PCR in bone marrow samples from children with T-ALL (n = 32) and common-ALL/pre-B ALL (n = 30). In pediatric ALL, higher expression levels of uc.112 were found in patients with T-ALL, compared to patients with B-ALL. T-cells did not differ significantly from B-cells regarding uc.112 expression in non-tumor precursors from public data. Additionally, among B-ALL patients, uc.112 was also found to be increased in patients with hyperdiploidy, compared to other karyotype results. The uc.122, uc.160, and uc.262 were not associated with biological or clinical features. These findings suggest a potential role of uc.112 in pediatric ALL and emphasize the need for further investigation of T-UCR in pediatric ALL.

Molecular Features of Three Children Diagnosed With Early T-Cell Precursor Acute Lymphoblastic Leukemia

No abstract available.

Clathrin Assembly Lymphoid Myeloid Leukemia-AF10-positive Acute Leukemias: A Report of 2 Cases with a Review of the Literature / 대한진단검사의학회지

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.

A Novel Translocation t(1;5)(p32;q31) that Was Not Associated with the TAL1 Rearrangement in a Case of T Lymphoblastic Leukemia/Lymphoma / 대한진단검사의학회지

Chromosome 1 band p32 (1p32) aberrations are common in T lymphoblastic leukemia/lymphoma (T-ALL/LBL). Two types of 1p32 aberrations include translocations with different partners and submicroscopic interstitial deletion. Both aberrations are known to result in TAL1 gene deregulation. The t(1;5)(p32;q31) is a rare translocation of 1p32 in T-ALL. We now present the second case of t(1;5)(p32;q31) in T-ALL, which was present as a primary cytogenetic abnormality, with a review of the relevant literature. Interestingly, neither the translocation of the TAL1 gene nor aberrant expression of TAL1 protein was detected by fluorescent in situ hybridization (FISH) and by immunohistochemical staining in this case.

Dificuldade diagnóstica em dois casos de neoplasia de células linfóides precursoras cutâneas primárias / Diagnostic pitfalls in two cases of primary cutaneous neoplasia of precursor lymphocytes

O linfoma linfoblástico (LLB) é uma neoplasia maligna de linfócitos precursores (B, T ou células NK). O comprometimento primário da pele é raro. Relatamos as características clínicas, anatomopatológicas e imunofenotípicas em dois pacientes com apresentação cutânea primária que, histologicamente, apresentavam infiltrado de células imaturas. A análise imunofenotípica foi realizada com amplo painel de anticorpos. A pesquisa de rearranjo no gene do receptor de células T (TCR-gama) pelo método de reação em cadeia da polimerase (PCR) resultou positiva em um caso, que era CD56 positivo, classificado como linfoma de células NK blásticas-símile. Este caso representa uma entidade distinta derivada de células precursoras num estágio precoce de uma via comum de diferenciação para células T e NK. O outro caso foi classificado como LLB-T com expressão aberrante de CD79a, o que poderia ser erroneamente interpretado. O diagnóstico correto depende da utilização de um amplo painel de anticorpos para caracterização imunofenotípica e avaliação molecular.

The lymphoblastic lymphoma (LBL) is a malignant neoplasm of precursor lymphocytes (B, T or NK-cells). The primary involvement of the skin is rare. We examined the clinical, anatomopathological and immunophenotypic features of two patients with primary cutaneous involvement. Histologically they showed an infiltrate of immature cells. The immunophenotypic analysis was performed with a comprehensive panel of antibodies. T-cell receptor rearrangement (TCR-gamma) was analyzed with polymerase chain reaction (PCR) and it was positive in one case, which was CD56 positive, classified as blastic NK-cell-like lymphoma. This case represents a distinct entity derived from precursor cells at an early stage of a common developmental pathway for T and NK cells. The other case was classified as T-cell lymphoblastic lymphoma with aberrant expression of CD79a, what could be a diagnostic pitfall. The accurate diagnosis depends on the use of a comprehensive panel of antibodies for immunophenotypic characterization and molecular analysis.

Does TAL-1 deletion contribute to the high incidence of T-cell acute lymphoblastic leukemia in South Indian patients?

BACKGROUND: The incidence of T-cell acute lymphoblastic leukemia (T-ALL) in South India is very high (43.1%) when compared to the Western countries (10-20%). TAL-1 deletion is the most common genetic abnormality in T-ALL. OBJECTIVES: The present study was aimed to detect the incidence of type 1 and type 2 TAL-1 deletions and assess whether they might contribute to the high incidence of T-ALL in South India. MATERIALS AND METHODS: 45 cases of T-ALL (pediatric-32, adolescents-7 and young adults-6) were studied by DNA-PCR and sequencing. Age of the patients ranged from 3 yrs to 29 yrs (median age 14 yrs). RESULTS: TAL-1 deletion type 1 was detected in 6 (13.3%) cases (3 pediatric and 3 adolescents) and all were males. TAL-1 deletion type 2 was not present. Comparing the clinical features and immunological marker analysis of TAL-1 deletion positive and negative cases did not show any significant differences except in the WBC count, which was significantly higher in cases showing TAL-1 deletion (>100 x 109/L, p value= 0.003). All the positive cases of TAL-1 deletion were confirmed by sequencing, the results showing that the fusion region at SIL gene and TAL-1 gene contained an average 'N region' insertion of 7.8 nucleotides. The numbers of nucleotides deleted at the 5' end and 3' end of TAL-1 gene were averages of 3 and 1, respectively. CONCLUSION: Though the incidence of T-ALL is high in South India, the frequency of TAL-1 deletion and their fusion gene sequences are not unique and are similar to those reported in other ethnic and geographic populations. Hence the present study indicates that TAL-1 deletion alone does not contribute to the high incidence of T-ALL in South Indian patients.

The significance of phenotyping leukemias using monoclonal antibodies

1. Acute leukemias have been defined as major types as of lymphoblastic and myeloblastic leuckemias according to morphological and cytochemical criteria. 2. The thecnical improvements and standardization of immunofluorescence and immunocytology staining methods have provied new insights for classifying these disorders on the basis of monoclonal antibodies. 3. The scheme used to describe normal lymphoid and myeloid differentiation, when also used to describe their malignant counterparts, provides a well-established model for the immunological classification of acute leukemias. 4. In this review article, we suggest some guidelines for performing a series of cytochemical reactions using immunological markers to ensure a reliable diagnosis of acute leukemia