Telomeric repeat-containing RNA is dysregulated in acute myeloid leukemia.

TERRA (telomeric repeat-containing RNA) is a class of long noncoding RNAs transcribed from subtelomeric and telomeric regions. TERRA binds to the subtelomeric and telomeric DNA-forming R-loops (DNA-RNA hybrids), which are involved in telomere maintenance and telomerase function, but the role of TERRA in human cells is not well characterized. Here, we comprehensively investigated for the first time TERRA expression in primary human hematopoietic cells from an exploratory cohort of patients with acute myeloid leukemia (AML), patients with acute lymphoblastic leukemia (ALL), patients with telomere biology disorder (TBD), and healthy subjects. TERRA expression was repressed in primary human hematopoietic cells, including healthy donors, patients with ALL, and patients with TBD, irrespective of their telomere length, except for AML. A second cohort comprising 88 patients with AML showed that TERRA was overexpressed in an AML subgroup also characterized by higher R-loop formation, low TERT and RNAseH2 expression, and a paucity of somatic splicing factor mutations. Telomere length did not correlate with TERRA expression levels. To assess the role of TERRA R-loops in AML, we induced R-loop depletion by increasing RNAseH1 expression in 2 AML cell lines. Decreased TERRA R-loops in AML cell lines resulted in increased chemosensitivity to cytarabine. Our findings indicate that TERRA is uniformly repressed in primary human hematopoietic cells but abnormally expressed in an AML subset with low telomerase.

Chemotherapy-Induced Peripheral Neuropathy Impacts Quality Of Life And Activities Of Daily Living Of Brazilian Multiple Myeloma Patients.

BACKGROUND: Survival in multiple myeloma (MM) has improved in the past years with the introduction of immunomodulators and proteasome inhibitors. However, chemotherapy-induced peripheral neuropathy (CIPN) is associated with both drug classes affecting Health-Related Quality of Life (HRQoL) and activities of daily living (ADL). OBJECTIVE: We evaluated CIPN in MM patients to identify associated factors and impacts on HRQoL and ADL. METHODS: This is a cross-sectional study with Brazilian patients from public and private health services. Patients were interviewed using validated tools to measure CIPN and HRQoL, along with sociodemographic and clinical questions. Logistic regression was used to assess the association of CIPN with sociodemographic, clinical, and HRQoL variables. RESULTS: In total, 217 patients were eligible for the study. The median age was 67, 50.9% were women, 51.6% had low income, 47.5% had low education, and 55.3% attended private health services. The chemotherapy regimen most used was the combination of cyclophosphamide, thalidomide, and dexamethasone (17.5%) among the 24 types of regimens found. Most patients (90.3%) had at least one CIPN symptom: 62.7% were severe, and 51.62% were extremely bothered ADL. Numbness was the most common symptom (40.6%). CIPN was independently associated with education, hospitalization, chemotherapy, side effects, disease symptoms, and global health status in HRQoL. CONCLUSION: MM patients showed a high frequency of CIPN, which affected ADL and impaired HRQoL. Early and accurate detection of CIPN and dose management in patients with thalidomide and bortezomib-based regimens should be performed to provide better treatment outcomes and avoid permanent disabilities.

Acute promyelocytic leukemia presenting as an extradural mass

Acute promyelocytic leukemia is potentially a highly curable type of leukemia that usually presents with pancytopenia, coagulopathies and bleeding. We describe a case of an unusual presentation of acute promyelocytic leukemia. A 53 year-old male was admitted complaining of pain and weakness in his legs. He presented at examination a spastic paraparesis with a sensitive level at the eighth thoracic medullar (T8) segment. Magnetic resonance imaging showed a posterolateral extradural mass from T6 through T8 segments with medullar compression. A complete blood count showed anemia, thrombocytopenia and the presence of promyelocytes and blasts. Marrow examination was compatible with the diagnosis of acute promyelocytic leukemia by cytogenetics and polymerase chain reaction for the PML-RARα gene. He was treated with all-trans-retinoic acid therapy plus daunorubicin and presented an all-trans-retinoic acid syndrome. Despite hematological remission, the patient presented neurologic deterioration and had to be treated with radiotherapy (total dose 3000 cGy) of the extradural lesion. The patient evolved with severe sepsis and died without any recovery from his neurologic deficit. Extramedullary infiltration is a very rare complication in acute promyelocytic leukemia. Most cases are related to relapse after initial treatment with all-trans-retinoic acid. The skin and the central nervous system are the most frequently involved sites. This is possibly the first case reported of this condition in which the patient had a symptomatic extradural mass.

Acute promyelocytic leukemia presenting as an extradural mass.

Acute promyelocytic leukemia is potentially a highly curable type of leukemia that usually presents with pancytopenia, coagulopathies and bleeding. We describe a case of an unusual presentation of acute promyelocytic leukemia. A 53 year-old male was admitted complaining of pain and weakness in his legs. He presented at examination a spastic paraparesis with a sensitive level at the eighth thoracic medullar (T8) segment. Magnetic resonance imaging showed a posterolateral extradural mass from T6 through T8 segments with medullar compression. A complete blood count showed anemia, thrombocytopenia and the presence of promyelocytes and blasts. Marrow examination was compatible with the diagnosis of acute promyelocytic leukemia by cytogenetics and polymerase chain reaction for the PML-RARα gene. He was treated with all-trans-retinoic acid therapy plus daunorubicin and presented an all-trans-retinoic acid syndrome. Despite hematological remission, the patient presented neurologic deterioration and had to be treated with radiotherapy (total dose 3000 cGy) of the extradural lesion. The patient evolved with severe sepsis and died without any recovery from his neurologic deficit. Extramedullary infiltration is a very rare complication in acute promyelocytic leukemia. Most cases are related to relapse after initial treatment with all-trans-retinoic acid. The skin and the central nervous system are the most frequently involved sites. This is possibly the first case reported of this condition in which the patient had a symptomatic extradural mass.

Valor do suporte nutricional em leucemia não-linfocítica aguda do adulto / The value of nutritional support in accute nonlymphocytic leukemia in adult

Vinte e cinco pacientes portadores de leucemia não -linfocítica aguda (LNLA) submetidos a 32 ciclos de quimioterapia (QT) com esquema padrão de Ara-C e daunoblastina foram acompanhados pelo Grupo de Suporte Nutricional do Serviço de Gastroenterologia, Nutrição e Cirurgia do Aparelho Digestivo do Hospital das Clínicas da UFMG. As intervenções nutricionais utilizadas foram dieta oral orientada em 11 ciclos (34,4 porcento) e dieta oral orientada mais nutrição parenteral em 21 ciclos (65,6 porcento). Os desfechos avaliados (remissão, falha terapêutica e óbito) não foram afetadas pelo tipo de suporte nutricional utilizado, embora o aporte calórico do grupo em nutrição parenteral (NP) e dieta oral orientada tenha sido inferior ao do grupo em dieta oral exclusiva. Os parâmetros de avaliação nutricional ao início da QT não parecem ter afetado os desfechos clínicos, mas correlacionaram-se significativamente com a indicação de NP. A albumina sérica ao término da QT correlacionou-se significativamente com os desfechos negativos. As doses de Ara-C não tiveram relação com mortalidade, mas os pacientes que receberam Ara-C em altas doses tiveram mais indicação de NP. Apesar do material não permitir conclusões definitivas, alguns pontos parecem ter tido relevância e mereceriam maiores discussões: a) a utilização de NP não afetou os desfechos clínicos; b) altas doses de Ara-C dificultam a ingesta oral adequada e aumentam a indicação de NP; c) o estado nutricional inicial não afetou os desfechos terapêuticos.