Inés Rodríguez-Hernández

Immunophenotypic, cytogenetic, and mutational characterization of cell lines derived from myelodysplastic syndrome patients after progression to acute myeloid leukemia

Leukemia cell lines have been widely used in the hematology field to unravel mechanistic insights and to test new therapeutic strategies. Myelodysplastic syndromes (MDS) comprise a heterogeneous group of diseases that are characterized by ineffective hematopoiesis and frequent progress to acute myeloid leukemia (AML). A few cell lines have been established from MDS patients after progression to AML but their characterization is incomplete. Here we provide a detailed description of the immunophenotypic profile of the MDS‐derived cell lines SKK‐1, SKM‐1, F‐36P; and MOLM‐13. Specifically, we analyzed a comprehensive panel of markers that are currently applied in the diagnostic routine for myeloid disorders. To provide high‐resolution genetic data comprising copy number alterations and losses of heterozygosity we performed whole genome single nucleotide polymorphism‐based arrays and included the cell line OHN‐GM that harbors the frequent chromosome arm 5q deletion. Furthermore, we assessed the mutational status of 83 disease‐relevant genes. Our results provide a resource to the MDS and AML field that allows researchers to choose the best‐matching cell line for their functional studies.

CD11b Expression in Acute Promyelocytic Leukemia

To the Editor Although the unequivocal diagnosis of acute promyelocytic leukemia (APL) is established by the finding of t(15;17) and/or the PML / RARA fusion gene, cytogenetic and molecular techniques are time-consuming. Instead, flow cytometry (FC) allows a prompt diagnosis of this form of leukemia and the rapid institution of the specific therapy. Several studies have tried to identify the panel of markers that better characterize this entity. In a series of 149 patients with APL, Dong et al1 found as constant the triple negativity for HLA-DR, CD11b, and CD11c. Similar results were obtained in a shorter study that analyzed 16 cases of APL,2 in which 100% of the patients were negative for CD34, CD14, and CD11b (CD11c was not studied). We hereby share a different experience in a similar study. The expression of CD34, CD11b, and DR, among other markers, was analyzed by FC in a retrospective series (years 2008–2013) of 18 patients (7 …

Scoring Systems in Mantle Cell Lymphoma: A Critical Point of View

A proposal for a scoring system in the diagnosis of chronic lymphoproliferative diseases other than CLL has been recently published in Cytometry Part B. The authors apply this score for deciding whether or not FISH evaluation for the detection of IGH/CCND1 rearrangements must be performed to exclude Mantle Cell Lymphoma (MCL). In their validation series, no MCL scored <3. We have applied their system to our cases of MCL and also to a small series of Marginal Zone lymphomas. In our hands, the scoring system as has been published does not discriminate adequately between both entities. We propose using the negativity of a marker, CD11c, instead of the platelet count to improve the results. However, we believe that given the clinical and prognostic implications of the diagnosis of MCL, scoring systems should be greatly ameliorated prior to their generalized use.

Retinal vein occlusion and paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disorder associated with increased risk for thrombosis and reduced life expectancy. Retinal vein occlusion (RVO) is a frequent cause of vision loss but its relationship with PNH has not been studied systematically. Patients followed up for RVO in our ophthalmology department were screened for the presence of a PNH clone in peripheral blood by means of flow cytometry. The presence of other well-documented risk factors for RVO was also analyzed. In a series of 110 patients (54 males, median age of 67) we found no evidence of PNH. Most patients (97/110) had cardiovascular risk factors and/or hyperhomocysteinemia (67/110). Inherited thrombophilias were rare (three confirmed cases). Therefore, PNH does not appear to play a role in the development of RVO. However, this finding does not necessarily apply to young patients and/or those with no conventional risk factors for RVO, due to the low number of patients in these subgroups in our population.

Chronic proton pump inhibition therapy in the diagnostic accuracy of serum pepsinogen I and gastrin concentrations to identify pernicious anaemia

BACKGROUND Chronic use of proton pump inhibitors (PPIs) leads to increases in gastrin and pepsinogen-I serum concentrations. AIM To asses if chronic treatment with PPIs has an effect on serum gastrin and pepsinogen-I concentrations for the diagnosis of pernicious anaemia (PA). MATERIALS AND METHODS Serum gastrin and pepsinogen-I were measured in 38 patients with PA and 74 without PA (controls); 17/38 PA patients and 36/74 controls were treated with PPIs. Receiver Operating Curves (ROC) were used to compare diagnostic accuracy of gastrin and pepsinogen-I for PA in patients under chronic treatment with PPIs and in untreated patients. RESULTS PPI treatment increased pepsinogen-I in patients and in controls, while gastrin increased only in controls. In untreated patients, a pepsinogen-I <8.3ng/mL had 95.2% sensitivity and 100% specificity, whereas a gastrin >115pg/mL had 100% sensitivity and 92.11% specificity for PA diagnosis. In PPI-treated patients, a pepsinogen I<24.1ng/mL had a lower sensitivity (82.4%) but retained 100% specificity, however the best cut-off point for gastrin, 610pg/mL, had a very low sensitivity (58%). CONCLUSIONS PPI chronic treatment decreased the diagnostic accuracy for the studied biomarkers, particularly of gastrin. In PPI-treated patients, serum pepsinogen-I concentrations >24.1ng/mL allowed rejecting a PA diagnosis with 100% specificity.

CD34 expression and the outcome of nucleophosmin 1-mutated acute myeloid leukemia.

CD34 positivity has been considered as an adverse prognostic factor in acute myeloid leukemia (AML). Although nucleophosmin 1-mutated (NPM1m) AML is usually CD34 negative, this marker may be expressed at diagnosis or acquired at relapse in a variable number of cases. Our objective was to ascertain if CD34 expression has any influence on the general outcome of this form of acute leukemia. Analysis of clinical outcome (complete remissions, relapses, disease-free survival, and overall survival) was performed depending on the degree of expression of CD34 determined by flow cytometry, in 67 adult patients with NPM1m AML. CD34 expression did not have any influence on the variables analyzed whatever the percentage of blasts expressing this marker. In contrast to other forms of AML, CD34 expression is not an unfavorable prognostic factor in NPM1m AML, neither at diagnosis nor at relapse.