Lineage switch of acute myeloid leukemia to T-Cell acute lymphoblastic leukemia – A unique case report

“Lineage switch” is term described when leukemic cells on relapse exhibit a new phenotype, where losses of one lineage defining markers with simultaneous gain of another lineage defining markers occur. Relapse of acute leukemia is although a very common event, lineage switch occurs and reported very rarely in such cases. The pathogenesis involved in this phenomenon remains unclear; however plasticity of hematopoietic progenitor affected by intrinsic and extrinsic environmental cues can be a possible explanation. In most of the cases at the time of relapse conversion of B-acute lymphoblastic leukemia (ALL) to acute myeloid leukemia (AML) occurs. Here, we presented an unusual case of 10 year old boy with AML switched to T-ALL upon relapse, which is very rare and not well documented till date in literature. The diagnosis was further supported by morphologic, cytochemistry and flowcytometric immunophenotyping (FCM-IPT). Prognosis and survival of such cases remains poor even by the use of standard chemotherapy.

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.

Childhood T-cell acute lymphoblastic leukemia in a single Latin American center: impact of improved treatment scheme and support therapy on survival

ABSTRACT Background and objective T-cell acute lymphoblastic leukemia (T-ALL) in children represents a high-risk disease. There is a lack of studies assessing the outcome of T-ALL in Hispanic populations, in which it is a rare malignancy. We report the characteristics and results of treatment for childhood T-cell ALL in children over 14 years at a Latin American reference center. Material and methods From January 2005 to December 2018, there occurred the analysis of twenty patients ≤ 16 years of age from a low-income open population diagnosed at a university hospital in Northeast Mexico. Clinical and laboratory characteristics, treatment regimens and outcomes were assessed by scrutinizing clinical records and electronic databases. Diagnosis was confirmed by flow cytometry, including positivity for CD-2, 5, 7 and surface/cytoplasmic CD3. Survival rates were assessed by the Kaplan-Meier method. Results There was a male preponderance (70 %), with a 2.3 male-to-female ratio (p= .074), the median age being 9.5 years. Leucocytes at diagnosis were ≥ 50 × 109/L in 13 (65 %) children, with CNS infiltration in 6 (30 %) and organomegaly in 10 (50 %). The five-year overall survival (OS) was 44.3 % (95 % CI 41.96-46.62), significantly lower in girls, at 20.8 % (95 % CI 17.32-24.51) vs. 53.1 % (95 % CI 50.30-55.82), (p= .035) in boys; there was no sex difference in the event-free survival (EFS) (p= .215). The survival was significantly higher after 2010 (p= .034). Conclusion The T-cell ALL was more frequent in boys, had a higher mortality in girls and the survival has increased over the last decade with improved chemotherapy and supportive care.

Alteration of NOTCH1 in T-cell Acute Lymphoblastic Leukemia and Development of Target Therapeutic Agent / 임상소아혈액종양

T-cell acute lymphoblastic leukemia (T-ALL) accounts for approximately 10-15% of entire ALL in children. The outcome of T-ALL has been improved through the intensified therapeutic strategy, however, it is still a more aggressive disease. In T-ALL a couple of transcription factor oncogenes are known to be relocated to the juxtaposition of T-cell receptor genes, potent promoter, by chromosome translocation. However the incidence of each chimeric gene formation in T-ALL is less than 5% and their clinical significance as a prognostic marker is lacking. A decade ago it was identified that activating mutations in NOTCH1 in about 60% of T-ALL. After then, activating NOTCH1 mutations present in T-ALL have been extensively investigated with regard to understanding its molecular pathogenesis, its prognostic significance, and developing molecularly tailored novel agents. Small molecule gamma-secretase inhibitor, blocking a proteolytic step required for creation of a fragment of NOTCH intracellular domain which actually act as a controller of its target gene expression, was tried as a target therapeutic drug for T-ALL. Although outcome of this drug was not satisfactory, challenges have been launched to develop new drugs which specifically act on the aberrant behavior of mutated NOTCH1 in T-ALL.

Alteration of NOTCH1 in T-cell Acute Lymphoblastic Leukemia and Development of Target Therapeutic Agent / 임상소아혈액종양

T-cell acute lymphoblastic leukemia (T-ALL) accounts for approximately 10-15% of entire ALL in children. The outcome of T-ALL has been improved through the intensified therapeutic strategy, however, it is still a more aggressive disease. In T-ALL a couple of transcription factor oncogenes are known to be relocated to the juxtaposition of T-cell receptor genes, potent promoter, by chromosome translocation. However the incidence of each chimeric gene formation in T-ALL is less than 5% and their clinical significance as a prognostic marker is lacking. A decade ago it was identified that activating mutations in NOTCH1 in about 60% of T-ALL. After then, activating NOTCH1 mutations present in T-ALL have been extensively investigated with regard to understanding its molecular pathogenesis, its prognostic significance, and developing molecularly tailored novel agents. Small molecule gamma-secretase inhibitor, blocking a proteolytic step required for creation of a fragment of NOTCH intracellular domain which actually act as a controller of its target gene expression, was tried as a target therapeutic drug for T-ALL. Although outcome of this drug was not satisfactory, challenges have been launched to develop new drugs which specifically act on the aberrant behavior of mutated NOTCH1 in T-ALL.

Effect of Hes1 on bone marrow CD34+cells in acute myeloid leukemia / 中国肿瘤临床

Objective:To determine the effect of Hes1 on bone marrow CD34+cells in acute myeloid leukemia (AML). Meth-ods:Bone marrow mononuclear cells were isolated by using Ficoll. Then, the proportion and cell cycle of CD34+cells were analyzed by using fluorescence-activated cell sorting (FACS). CD34+cells were cultured in vitro for colony-forming cells (CFC). The expression of Hes1 in CD34+cells was evaluated by using real-time polymerase chain reaction. After upregulating the expression of Hes1 in CD34+cells, the cell cycle was analyzed through FACS, and the colony formation of CD34+Hes1+cells was analyzed by CFC. Results:The ra-tio of CD34+cells in the bone marrow was lower in the AML group than in the control group. In addition, more CD34+cells underwent quiescence in the AML group than in the control group. In vitro assay showed that the colony formation of CD34+cells was lower in the AML group than in the control group. The expression of Hes1 was higher in the CD34+cells from the AML patients than that in the CD34+ cells from normal donors. After Hes1 transduction, more CD34+ cells underwent quiescence and showed weak proliferation. Conclusion:The proportion of CD34+cells in the bone marrow was lower in AML patients than in normal donors. A large proportion of CD34+cells underwent quiescence, which was related to Hes1, in AML patients.

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.

The changes of functions of chemokine receptor 9 on T cell lymphocytic leukemia patients / 中国免疫学杂志

Objective:To observe the influences of functions of chemokine receptor 9(CCR9) on leukemia patients,we analyzed 38 typical T cell lymphocytic leukemia cases.Methods:The functions of T ALL and T CLL CD4+T cells towards TECK/CCL25 were determined by chemotaxis assay and adhesion assay.Results:Almost in all of the T ALL patients,TECK/CCL25(a ligand for CCR9)could induce a high chemotactic migration of T ALL CD4+ cells as well as a high adhesion.Conclusion:It indicates that CCR9 and its ligands may promote survival or proliferation of T ALL cells. [

Classification and Prognostic Significance of Immunophenotypic Subgroups in Non-T-ALL(I) / 대한임상병리학회지

BACKGROUND: Recently, the importance of immunologic subclassification based on surface marker expression of acute lymphoblastic leukemia (ALL) has been emphasized. The importance of immunophenotypic analysis of ALL has been documented by numerous studies, but study for survival rate of subgroups in the non-T-ALL was rarely documented in Korea. The aim of this study was to classify the non-T-ALL immunologically, and to compare the survival rates among the subgroups. MATERIALS AND METHODS: From April, 1987 to October, 1997, 142 patients diagnosed as non-T- ALL by immunophenotyping were classified into 6 subgroups, group I to group VI. Review of medical records were undertaken in 130 patients and analysed for survival rates. For the cases in whom CD20 not tested, classification was also undertaken into 4 groups. The survival analysis of immunophenotypic subgroups was carried out by Kaplan-Meier method and differences in survival rates were tested by the log-rank test. RESULTS: The 142 patients, which included patients in whom CD20 was not tested, were assigned into 4 groups as follows: Group I (2 cases, 1%), Group II (24 cases, 17%), Group III-V (110 cases, 78%), Group VI (6 cases, 4%). On the other hand, 113 patients in whom CD20 was tested, were assigned into 6 groups as follows: Group I (0 cases, 0%), Group II (22 cases, 20%), Group III (59 cases, 52%), Group IV (23 cases, 21%), Group V (3 cases, 3%), Group VI (5 cases, 4%). The result showed that median survival time was higher in Group III and Group III-V, and lower in Group VI. However, statistic difference was not seen for 6 subgroups, while in the study for 4 subgroups, statistic difference was seen (p=0.04). And in children, study for 6 subgroups and 4 subgroups showed statistic differences in survival rate. CONCLUSIONS: We conclude that immunophenotypic subclassification of Non-T-ALL is a valuable prognostic marker in children.