Philadelphia-positive case negative for JAK2 V617F mutation with hyperdiploidic karyotype: A case report.

Chronic myeloid leukemia (CML) is one of the most common hematological malignancies and accounts for 15-20% of all leukemia cases. The cytogenetic marker of CML is the presence of Philadelphia chromosome (Ph) in >95% of patients. The current case reports a 83-year old woman who was directed to the genetic laboratory for a cytogenetic and molecular-genetic analysis suspected to be Ph positive [(+)]. Karyotype analysis of a bone marrow sample revealed a hyperdiploid karyotype in a part of Ph (+) cells with additional chromosomes 8, 10 and 12. Restriction analysis for V617F JAK2 mutation was negative, while the quantitative RT-qPCR assay indicated BCR-ABL/ABL transcript at the level of 120% International Scale (IS). Generally cytogenetic complexities are important in the prognostic evaluation of CML. Besides the Ph chromosome, a variet of chromosomal aberrations may be associated with CML. A total of 5-10% of these cases show complex translocations involving another chromosome. The current case is Ph(+) demonstrating an additional hyperdiploid karyotype clone with three additional autosomes (8, 10 and 12). This case highlights the significance of cytogenetic abnormalities on the prognosis of CML.

Three cases of non-Hodgkin's lymphoma in HIV-infected Bulgarian patients.

HIV-associated lymphoma was first classified as an AIDS-defining disease by the American Center for Disease Control and Prevention (CDC) in 1985. Non-Hodgkin's lymphomas (NHLs) are frequent malignancies in AIDS patients. The risk of NHL in the case of an underlying HIV infection is estimated to be 100 times greater than in the general population, and it increases with the progression of the retrovirus-related immunosuppression. Cases of HIV-related non-Hodgkin's lymphoma are widely documented in the literature. In this article we present three cases of NHL and HIV hospitalized over a period of three years (2013-2016) at our specialized department for AIDS patients. Two of them were initially diagnosed with NHL and then with HIV infection. In one patient, NHL developed despite the patient's taking background antiretroviral therapy. The first case was a 38-year-old male diagnosed previously with HIV, who developed a palpable mass in the left zygomatic bone. The second case was a 52-year-old male who was first diagnosed with a cutaneous lymphoma, and subsequently with HIV infection. The third patient was a 63-year-old male who presented with two palpable masses: one in the left part of the mandible, and the other in the right inguinal region, the latter subsequently diagnosed as lymphoma. Following the latter diagnosis, the patient tested positive for HIV. The histological findings of the three lymphomas were as follows: an NHL plasmoblastic lymphoma, a cutaneous large B-cell anaplastic lymphoma, and a diffuse large B-cell lymphoma. The first patient received antiretroviral therapy (ART) and EPOCH (etoposide, pharmarubicin, vincristin, endoxane, uromitexan) plus radiotherapy, while the second received ART and CHOEP (endoxan, epirubicin, vincristin, etoposide, prednisolone). The third patient died a few days after beginning antiretroviral therapy.

NPM1 Gene Type A Mutation in Bulgarian Adults with Acute Myeloid Leukemia: A Single-Institution Study.

OBJECTIVE: Mutations of the nucleophosmin (NPM1) gene are considered as the most frequent acute myeloid leukemia (AML)-associated genetic lesion, reported with various incidences in different studies, and type A (NPM1-A) is the most frequent type. However, since most series in the literature report on the features of all patients regardless of the type of mutation, NPM1-A(+) cases have not been well characterized yet. Therefore, we evaluated the prevalence of NPM1-A in Bulgarian AML patients and searched for an association with clinical and laboratory features. MATERIALS AND METHODS: One hundred and four adults (51 men, 53 women) were included in the study. NPM1-A status was determined using allele-specific reverse-transcription polymerase chain reaction with co-amplification of NPM1-A and ß-actin and real-time quantitative TaqMan-based polymerase chain reaction. Patients received conventional induction chemotherapy and were followed for 13.2±16.4 months. RESULTS: NPM1-A was detected in 26 (24.8%) patients. NPM1-A mutation was detected in all AML categories, including in one patient with RUNX1-RUNX1T1. There were no differences associated with the NPM1-A status with respect to age, sex, hemoglobin, platelet counts, percentage of bone marrow blasts, splenomegaly, complete remission rates, and overall survival. NPM1-A(+) patients, compared to NPM1-A(-) patients, were characterized by higher leukocyte counts [(75.4±81.9)x109/L vs. (42.5±65.9)x109/L; p=0.049], higher frequency of normal karyotype [14/18 (77.8%) vs. 26/62 (41.9%); p=0.014], higher frequency of FLT3-ITD [11/26 (42.3%) vs. 8/77 (10.4%); p=0.001], and lower incidence of CD34(+) [6/21 (28.8%) vs. 28/45 (62.2%); p=0.017]. Within the FLT3-ITD(-) group, the median overall survival of NPM1-A(-) patients was 14 months, while NPM1-A(+) patients did not reach the median (p=0.10). CONCLUSION: The prevalence of NPM1-A mutation in adult Bulgarian AML patients was similar to that reported in other studies. NPM1-A(+) patients were characterized by higher leukocyte counts, higher frequency of normal karyotypes and FLT3-ITD, and lower incidence of CD34(+), supporting the idea that the specific features of type A mutations might contribute to the general clinical and laboratory profile of NPM1(+) AML patients.