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Characterization of miRNomes in acute and chronic myeloid leukemia cell lines.

Myeloid leukemias are highly diverse diseases and have been shown to be associated with microRNA (miRNA) expression aberrations. The present study involved an in-depth miRNome analysis of two human acute myeloid leukemia (AML) cell lines, HL-60 and THP-1, and one human chronic myeloid leukemia (CML) cell line, K562, via massively parallel signature sequencing. mRNA expression profiles of these cell lines that were established previously in our lab facilitated an integrative analysis of miRNA and mRNA expression patterns. miRNA expression profiling followed by differential expression analysis a…

[Nilotinib in patients with chronic myeloid leukemia without response to imatinib].

BACKGROUND: Resistance and intolerance to imatinib in patients with chronic myeloid leukemia requires alternative therapies. Nilotinib provides a choice as a second-line treatment. The objective of this report was to show the results of a group of patients with chronic myeloid leukemia who received nilotinib as a second-line treatment. METHODS: The medical records of 16 patients of both sexes, of any age, diagnosed with chronic myeloid leukemia, who received nilotinib as a second-line treatment, were reviewed. All of them had received imatinib prior as first-line treatment; the causes to swit…

[Congenital dysfibrinogenemia coincidentally diagnosed at the onset of chronic myelogenous leukemia].

A 34-year-old man was referred to our hospital for leukocytosis and fundal hemorrhage. Peripheral blood and coagulation tests showed increases in cells at all stages of the neutrophilic series and a low level of fibrinogen (Fbg). Chronic myelogenous leukemia (CML) was diagnosed, and nilotinib was administered. During the clinical course of CML treatment, plasma Fbg levels continued to be low, but the patient showed neither hemorrhagic nor thrombotic complications. Fbg analysis showed normal antigen levels and low activity levels, which indicated dysfibrinogenemia. Genetic analysis revealed a h…

BMI1 gene expression in myeloid leukemias and its impact on prognosis.

BACKGROUND: BMI1 is a polycomb group (PcG) protein and is overexpressed in leukemia. It plays a key role in the self-renewal of stem cells. Leukemic cells lacking BMI1 underwent proliferation arrest and showed signs of differentiation and apoptosis. AIM: This study was aimed to investigate the expression and impact of BMI1 in myeloid leukemias. Expression levels of BMI1 in 100 acute myeloid leukemia (AML), 100 chronic myeloid leukemia (CML) patients and 20 healthy controls were measured by real time quantitative polymerase chain reaction (RQ-PCR). RESULTS: The results showed that the express…

[SHP-1 gene in the disease progression of chronic myeloid leukemia].

OBJECTIVE: To investigate the profile of promoter methylation and expression of SHP-1 gene in the progression of chronic myeloid leukemia (CML). METHODS: The expression level of SHP-1 mRNA and protein in bone marrow or peripheral blood mononuclear cells from CML patients were detected by Western blot and SYBR Green-based qRT-PCR. The methylation status of SHP-1 were assessed by methylation-specific polymerase chain reaction (MSP) assay. K562 cells were infected with the lentiviral plasmids pEX-SHP-1-puro-Lv105 (K562-SHP-1) or pEX-EGFP-puro-Lv105 (K562-EGFP). The levels of proteins and phospho…

The genomic landscape of acute lymphoblastic leukemia in children and young adults.

Our understanding of the genetic basis of childhood acute lymphoblastic leukemia (ALL) has been greatly advanced by genomic profiling and sequencing studies. These efforts have characterized the genetic basis of recently described and poorly understood subtypes of ALL, including early T-cell precursor ALL, Philadelphia chromosome-like (Ph-like) ALL, and ALL with intrachromosomal amplification of chromosome 21, and have identified several rational therapeutic targets in high-risk ALL, notably ABL1-class and JAK-STAT inhibitors in Ph-like ALL. Deep sequencing studies are also refining our unders…

18F-FDG hepatic superscan in a patient with chronic myeloid leukemia.

A 62-year-old man with a history of breakpoint cluster region-ABL-positive chronic myeloid leukemia treated with hydroxyurea and interferon alfa for 4 years presented a lesion in the left lateral lobe of the liver. Besides an FDG-avid lesion, his 18F-FDG PET/CT study showed intense and diffuse FDG uptake (reminiscent of a hepatic superscan) throughout the rest of the left lobe and the right anterior lobe of the liver. This interesting superscan indicated that patients with chronic myeloid leukemia may show hepatic involvement by leukemia cells.

[Pregnancy and myeloid leukemia treated with imatinib. Development and monitoring of a patient].

BACKGROUND: Imatinib has changed the natural history of chronic myeloid leukemia. There are women with chronic myeloid leukemia in reproductive age with pregnancy desires. The aim of this case was to report the course and outcome of pregnancy in a patient with chronic myeloid leukemia diagnosis treated with imatinib. CLINICAL CASE: A 32 year old female with diagnosis of chronic myeloid leukemia with follow-up of 11 years. She received standard treatment, but she reported poor adherence; therefore, she received imatinib therapy two years after the diagnosis. The patient stopped the treatment h…

Eccrine poromatosis in a patient with acute myeloid leukemia following chemotherapy.

Eccrine poromas are rare, benign adnexal tumors that often occur as solitary papules. Rarely, eccrine poromas can present as multiple lesions, which is referred to as eccrine poromatosis. We report a case of eccrine poromatosis occuring on the palms and soles occuring after chemotherapy in a patient with a history of acute myeloid leukemia.

Melanoma in patients with chronic lymphocytic leukemia and non-Hodgkin lymphoma.

BACKGROUND: The relationship between melanoma and chronic lymphocytic leukemia (CLL) or non-Hodgkin lymphoma (NHL) has been minimally investigated. OBJECTIVE: The objective of this study was to examine the incidence of melanoma in patients with a history of CLL or NHL, and their associated mortality. METHODS: Cohorts of Kaiser Permanente Southern California members with a history of CLL and NHL were identified. Age-adjusted incidence density rates of melanoma among patients with CLL or NHL were compared with rates of melanoma among the general population of Kaiser Permanente Southern Califor…

A case of acute promyelocytic leukemia concomitant with plasma cell myeloma.

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… Am J Hematol 2002 71 94 97 12353307 10.1002/ajh.10167 4 Parapia L Abbott CR Masters GM Roberts BE Simultaneous presentation of acute myelomonocytic leukemia and multiple myeloma Acta Haematol 1982 68 153 156 6812372 10.1159/000206968 5 Raz I Polliack A Coexistence of myelomonocytic leukemia and monoclonal … myeloma and acute myeloid leukemia Indian J Pathol Microbiol 2008 51 118 120 18417881 10.4103/0377-4929.40422 9 Kim D Kwok B Steinberg A Simultaneous acute myeloid leukemia and multiple myeloma successfully treated with allogeneic stem cell transplantation South Med J 2010 103 1246 1249 21037523 10.1097 …

Fatal cardiac tamponade as the first manifestation of acute myeloid leukemia.

Acute myeloid leukemia is a hemopoietic myeloid stem cell neoplasm. It is the most common acute leukemia affecting adults,and its incidence increases with age. Acute myeloid leukemia is characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. As the leukemic cells keep filling the bone marrow, symptoms of the disease started to appear: fatigue, bleeding, increased frequency of infections, and shortness of breath. Cardiac tamponade or pericardial tamponade is an acute medical condition in which th…

Overexpression of EZH2 associates with a poor prognosis in chronic lymphocytic leukemia.

EZH2, a histone methyltransferase, is overexpressed in several human tumors, but whether it exerts any impact in chronic lymphocytic leukemia (CLL) remains unknown. We used real time PCR to investigate the expression profile of EZH1 and EZH2 in 59 CLL patients, 10 samples of purified B-cells from healthy donors and 12 normal adult tissues. EZH2 was overexpressed in CLL patients and correlates with high white blood cell count, ZAP-70 expression and chromosomal abnormalities. EHZ1 expression does not correlate with CLL progression. EZH2 overexpression is related to a poor prognosis of CLL and co…

Are GATA1 mutations occurring at random in Down syndrome transient leukemia?

The somatic mutation theory of cancer proposes that cancer begins with a somatic mutation occurring at random in a single cell that then passes the mutation to its progeny, generating a clone of premalignant cells. This clone leads to a full malignant tumor through additional mutations and selection processes. Strikingly, the best-documented human model of early oncogenesis, i.e., transient myeloproliferative disorder followed by acute megakaryoblastic leukemia (AMKL) in infants with Down syndrome (DS, or trisomy 21), exhibits important discrepancies with the SMT. Somatic mutations in megakary…

Pathologic rupture of the spleen in a patient with acute myelogenous leukemia and leukostasis.

Rupture of the spleen can be classified as spontaneous, traumatic, or pathologic. Pathologic rupture has been reported in infectious diseases such as infectious mononucleosis, and hematologic malignancies such as acute and chronic leukemias. Splenomegaly is considered the most relevant factor that predisposes to splenic rupture. A 66-year-old man with acute myeloid leukemia evolved from an unclassified myeloproliferative neoplasm, complaining of fatigue and mild upper left abdominal pain. He was pale and presented fever and tachypnea. Laboratory analyses showed hemoglobin 8.3g/dL, white blood …

Dasatinib: a guide to its use in chronic myeloid leukemia in the EU.

Oral dasatinib (Sprycel(®)) is effective in the treatment of patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML) or imatinib-resistant or imatinib-intolerant chronic-phase, accelerated-phase, or blast-phase CML. In particular, dasatinib is associated with better and faster responses than imatinib in patients with newly diagnosed chronic-phase CML. The response to dasatinib appears to be maintained in the longer-term. Dasatinib has an acceptable tolerability profile; it is associated with myelosuppression, with fluid retention being the most common nonhematologic adverse …

Management options for refractory chronic myeloid leukemia: considerations for the elderly.

Despite the excellent results obtained with standard-dose imatinib as first-line therapy for chronic myeloid leukemia in the chronic phase, one third of patients do not achieve an optimal response and require alternative therapies due to the emergence of drug resistance. Studies of resistance mechanisms, first tested in vitro and then in vivo, have driven the development of second-generation tyrosine kinase inhibitors (TKIs), dasatinib and nilotinib. These agents have been proven effective in a large number of patients resistant to imatinib and are also effective in older patients. The use of …