Appearance of estrogen positive bilateral breast carcinoma with HER2 gene amplification in a patient with aplastic anemia.

Immunosuppressive therapy is one of the standard therapy protocols for aplastic anemia (AA). However, immunosuppressive therapy and androgenic steroids can promote development of solid tumors such as squamous carcinoma, head and neck tumors, adenocarcinoma of the stomach, hepatocarcinoma and breast carcinoma in long surviving patients with aplastic anemia. We present here a rare case of a 56-year-old woman in whom bilateral adenocarcinoma of the breast developed 11 years after the start of immunosuppressive and androgenic steroid therapy for aplastic anemia. Histological examination showed invasive ductal carcinoma with intense nuclear staining for estrogen receptors. Her2 immunohistochemistry was positive for 80% of stained cells, and chromogenic in situ hybridization showed a high level of HER2 gene amplification. This case indicated that a new therapy option is needed for estimation and evaluation to avoid the consequence of cancer occurrence.

Induction chemotherapy versus palliative treatment for acute myeloid leukemia in a consecutive cohort of elderly patients.

A retrospective survey of 210 consecutive patients aged ≥ 65 years (median age 69 years, range 65-88 years) with acute myeloid leukemia (AML) diagnosed at a single center over a 6-year period (January 2001 to December 2006) is presented. De novo AML was diagnosed in 179 (85.2 %) patients and 31 (14.7 %) patients had a secondary AML. Twenty-three patients had M0 (11 %), 36 M1 (17.15 %), 57 M2 (27.1 %), eight M3 (3.8 %), 45 M4 (21.4 %), 31 M5 (14.8 %), one M6 (0.5 %), one M7 (0.5 %), and eight patients had unclassified myeloid leukemia (3.8 %) according to French-American-British (FAB) Study Group Classification. Eight patients with M3 (acute promyelocytic leukemia) were excluded from the study. Cytogenetic analysis was performed in 172/202 (85 %) patients. The normal karyotype was found in 81/172 (47 %), high risk aberrations in 32/172 (18.6 %), and favorable karyotype in 13/172 (7.5 %) patients. Supportive and palliative therapies were applied in 115 (56.9 %) patients, a no induction chemotherapy (NIC) group, and 87 (43.1 %) patients received induction chemotherapy (IC group). Complete remission (CR) was achieved in 45/87 (51.7 %) in the IC group and in 5/115 (4.3 %) in the NIC group of patients. After a median follow up of 4 years, 194 (96 %) patients died. The variables significantly associated with a longer overall survival (OS) by univariate analysis were an age of <75 years, a better ECOG performance status (PS) (p = 0.000, CI 95.0 %, 1.358-2.049), a serum LDH activity <600 U/l (p = 0.000, CI 95.0 %, 1.465-2.946), lower white blood cell (WBC) count at diagnosis (p = 0.011, CI 95.0 %, 1.102-2.100), lower comorbidity HCT-CI index (p = 0.000, CI 95 % 2.209-3.458), absence of splenomegaly (p = 0.015, CI 95.0 %, 1.082-2.102) and hepatomegaly (p = 0.008, CI 95.0 %, 1.125-2.171), and no preceding nonhematological malignancy. Multivariate analysis showed that significant factors affecting OS in the IC group were achievement of CR (p = 0.000), the ECOG PS (p = 0.045) and the ECOG PS (p = 0.000), and HCT-CI (p = 0.000) in the NIC group of elderly patients. The present study suggests that a subgroup of elderly patients with both ECOG PS and HCT-CI ≤ 2 at presentation may be eligible for intensive induction chemotherapy.

Prognostic impact of NPM1 mutations in Serbian adult patients with acute myeloid leukemia.

Based on current findings, the presence of NPM1 mutations in acute myeloid leukemia (AML) patients is associated with an increased probability of complete remission (CR) and better overall survival (OS). We determined the incidence and prognostic relevance of NPM1 mutations, their association with FLT3 and IDH mutations, and other clinical characteristics in Serbian adult AML patients. Samples from 111 adult de novo AML patients, including 73 AML cases with a normal karyotype (NK-AML), were studied. NPM1, FLT3, and IDH mutations were detected by PCR and direct sequencing. NPM1 mutations were detected in 22.5% of patients. The presence of NPM1 mutations predicted a low CR rate and shorter OS. NPM1 mutations showed an association with both FLT3 and IDH mutations. Survival analysis based on NPM1/FLT3 mutational status revealed a lower OS for NPM1(+)/FLT3(-) compared to the NPM1(-)/FLT3(-) group in NK-AML patients. The lack of impact or unfavorable prognostic effect of NPM1 mutations found in this study can be assigned to a small cohort of analyzed AML patients, as can the presence of FLT3 and IDH mutations or other genetic lesions that cooperate with NPM1 mutations influencing prognosis.

Alveolar granulocytic sarcoma of the mandible in a patient with HIV.

BACKGROUND: Granulocytic sarcoma (chloroma) occurs primarily in patients with acute myelogenous leukemia although it can also appear in connection with other myeloproliferative disorders. CASE REPORT: We present the case of a 52-year-old human immunodeficiency virus (HIV)-positive female patient with a CD4+ count of 321 cells/ml, who developed an alveolar granulocytic sarcoma of the mandible. Pathological analysis of the tumor mass showed an infiltrate of immature cells which were positive for CD13, CD33, CD15, CD11b, and CD64, and negative for CD34, CD117, and HLA-DR. The patient achieved complete remission following a 1-week course of chemotherapy, however, 7 months later she developed a second granulocytic sarcoma in the left soleus muscle. The absolute CD4+ count had now reduced to 3 cells/ml with an inversion in the Th/Ts index (0.01), and she died of gram-negative sepsis 1 month later. CONCLUSIONS: Granulocytic sarcoma is extremely rare in patients with HIV. The case is discussed with reference to the literature.

An aggressive extramedullary cutaneous plasmacytoma associated with extreme alterations in the innate immune system.

BACKGROUND: The role of natural killer (NK) cells in plasma cell diseases has not yet been fully characterized. CASE REPORT: We present the case of a 47-year-old man with an extremely aggressive extramedullary plasmacytoma of the lung with associated cutaneous lesions, whose disease was accompanied by a significantly decreased number of NK cells (CD56+, CD16+, CD3-) in the peripheral blood, very low NK cell activity levels, and a decreased interleukin-2 production from cultured cells in vitro. Histology and immunohistochemistry of the lung and cutaneous lesions identified that the tumor was composed of clonal plasma cells which were CD38+++, CD138+++, lambda chain+, kappa chain-, and cytokeratin-. Bone marrow histology and cytology were initially normal. The disease progressed rapidly despite local radiotherapy and systemic chemotherapy, and the patient died shortly after diagnosis. CONCLUSIONS: Cutaneous involvement in extramedullary plasmacytoma represents a clinically aggressive variant of plasma cell tumor, which runs a rapid course and has associated devastating effects on the patient's innate immune system.

More than a third of non-gastric malt lymphomas are disseminated at diagnosis: a single center survey.

Mucosa-associated lymphoid tissue (MALT) lymphomas are extranodal B-cell tumors that generally follow an indolent course. The gastrointestinal tract is the most common site of MALT lymphoma, comprising 50% of all cases. The tissue lesions are often localized, have high therapeutic response rates with late relapses with a long overall survival (OS). The patients with non-gastric lesions may follow a different clinical course and many of them present with disseminated disease. This study reports a series of 51 patients with non-gastric MALT lymphoma. Twenty patients (39.2%) presented with disseminated disease, seven (13.7%) patients had two MALT mucosal sites involved and eight (15.7%) had involvement of three or more mucosal sites. At presentation, 17 (33.3%) patients had the lymph node and 12 (23.5%) the bone marrow involvement. Following various combinations of treatment, complete remission was achieved in 40 (81.6%), and partial remission in three of the 49 treated patients with no difference in response rates between different disease stages. Relapse occurred in 12/43 (27.9%) patients among whom eight (18.6%) recurred in the presenting organ system. Five patients (9.8%) died because of a rapid disease progression after a median follow-up of 56 months; two patients with primary lung lesions, 1 patient with secondary intestinal disease, and 2 patients suffered transformation to diffuse large B-cell lymphoma. No significant difference in survival was found between localized and disseminated disease (log rank 0.05, df = 1, P = 0.81). A patient age > or = 60 yr at diagnosis and presentation with the nodal disease were found to be statistically significant negative prognostic factors (P < 0.05). Median OS was not reached after 145 months of follow-up, with the estimated OS being 88% at 2 yr, and 78% at 5 yr.

Elevated TNF-alpha and LDH without parathormone disturbance is associated with diffuse osteolytic lesions in leukemic transformation of myelofibrosis.

Myelofibrosis is a clonal myeloproliferative disorder characterized by splenomegaly, abnormal deposition of collagen in the bone marrow, extramedullary hematopoiesis, dacriocytosis, and leukoerythroblastic blood smear. Development and maintenance of fibrosis are mediated by a complex network of several cytokines, including tumor necrosis factor-alpha (TNF-alpha). Osteosclerosis is the most frequently observed bone change in myelofibrosis. Based on this, we present an atypical case of leukemic transformation in myelofibrosis associated with diffuse osteolytic lesions and extremely elevated TNF-alpha and lactate dehydrogenase (LDH). Parathormone was not disturbed.

Analysis of CD23 antigen expression in B-chronic lymphocytic leukaemia and its correlation with clinical parameters.

B-Chronic lymphocytic leukaemia (B-CLL) is a monoclonal malignancy characterized by an accumulation of terminally differentiated small and anergic B lymphocytes in the blood, bone marrow and other tissues. CD23 antigen, a trans-membrane glycoprotein, promotes the activation and proliferation of normal B lymphocytes and has an important role in the process of malignant transformation in B-CLL. This retrospective cohort study of 77 consecutive newly diagnosed B-CLL patients, 43 males, 34 females, median age of 62 years, examined CD23 expression and correlations with clinical parameters. CD23+ was negatively correlated with pro-lymphocyte infiltration of the bone marrow (P<0.01) and peripheral blood lymphocyte counts (P<0.001). Lower CD23 expression was correlated with lower serum immunoglobulin levels (P<0.05), especially IgG; while greater CD23 expression was positively correlated with higher CD5 levels. B-CLL patients with a percentage of CD23+ lymphocytes >40% had longer survival (92.8 months) than those expressing <40% (35.3 months) (P=0.001). CD23 is not uniformly expressed by lymphocytes in B-CLL patients, and the differences in expression are dependent on a number of clinical parameters, including the peripheral blood lymphocyte count and the degree of pro-lymphocyte infiltration of the bone marrow. CD23 expression is significantly decreased in patients with extremely high lymphocyte counts (PBL counts of >100 x 10(9)/l) and in the advanced stages of disease.

Thirty patients with primary plasma cell leukemia: a single center experience.

The primary plasma cell leukemia (PCL) is a rare aggressive plasma cell dyscrasia. We investigated its clinical and laboratory aspects in a large series of patients. Among 934 consecutive patients with multiple myeloma (MM), registered between 1978 and 2004 in a single institution, 30 patients [M/F: 22/8; median age (yr): 60, range: 36-79] with PCL (3.1%) were diagnosed. Retrospective analysis of the clinical, immunophenotypic, and cytogenetic aspects was performed. All patients had anemia, thrombocytopenia, circulating plasma cells (median count 4 x 10(9)/l), and in 18/30 patients hypercalcemia was found. Extramedullar involvement was present in 18/30 (60%) patients. The plasma cells were CD138+ and CD38+ (9/9), CD20+ (1/9), and CD10+ (1/9) with cytoplasmic positivity for light chains (9/9). The cytogenetic studies, evaluable in 21/30 patients, showed normal karyotype (6/21), complex hypodiploidy (6/15), pseudodiploidy (5/15), and hyperdiploidy (4/15). Treatment modalities had no impact on survival (median 4.5 months). Seven patients achieved remission. The performance status (ECOG >or= 2), platelet count or= 460 U/l were independent prognostic parameters of survival. The immunologic and cytogenetic presentation of patients with PCL bears little significance on prognosis, which is heavily compromised by advanced age at diagnosis and the poor performance status.

Nephrotic syndrome and acute renal failure in non-Hodgkin lymphoplasmacytic lymphoma.

Two patients with lymphoplasmacytic lymphoma, and monoclonal proteins of IgM in one, and IgG and lambda light chains in the second patient, nephrotic syndrome and acute renal failure are reported. A 58-year-old man previously treated for pre-B acute lymphoblastic leukemia, developed 3 years later nephrotic syndrome as a complication of lymphoplasmacytic lymphoma and high-paraprotein IgM kappa type. Immunofluorescent analysis of kidney biopsy showed extensive IgM and light kappa chain deposits, which caused membranoproliferative glomerulonephritis. Treatment with cyclophosphamide was ineffective and patient died 2 months later. The second patient is a 42-year-old female diagnosed with lymphoplasmacytic lymphoma and paraprotein IgG lambda type. The course of the disease was fulminant with developing nephrotic syndrome and fatal acute renal failure. Immunofluorescent and light microscopic studies of kidney biopsy showed signs of immunotactoid glomerulonephritis with deposits of IgG and C3. Hemodyalises and cytostatic therapy were without response and she died after 45 days.

Importance of early detection and follow-up of FLT3 mutations in patients with acute myeloid leukemia.

Mutations in the fms-like tyrosine kinase 3 (FLT3) gene, such as internal tandem duplication (FLT3/ITD) in the juxtamembrane domain and point mutations in the tyrosine kinase domain, are the most common abnormalities in acute myeloid leukemia (AML). FLT3/ITD and FLT3/D835 mutations were analyzed in 113 Serbian adult AML patients using polymerase chain reaction. Twenty patients were found to be FLT3/ITD positive (17.7%). The mutations occurred most frequently in M5 and M0 subtypes of AML. They were mainly associated with the normal karyotype. All patients harboring FLT3/ITD had a higher number of white blood cells than patients without it (p = 0.027). FLT3/ITD mutations were associated with lower complete remission (CR) rate (chi (2 )= 5.706; p = 0.017) and shorter overall survival (OS; Log rank = 8.76; p = 0.0031). As for disease-free survival, the difference between FLT3/ITD-positive and FLT3/ITD-negative patients was not statistically significant (Log rank = 0.78; p = 0.3764). In multivariate analysis, the presence of FLT3/ITD mutations was the most significant prognostic factor for both OS and CR rate (p = 0.0287; relative risk = 1.73; 95% CI = 1.06-2.82). However, in the group of patients with the intermediate-risk karyotype, the mere presence of FLT3/ITD was not associated with inferior clinical outcome. FLT3/D835 point mutation was found in four patients (3.5%) only. Follow-up of the FLT3/ITD-positive patients revealed stability of this mutation during the course of the disease. However, changes in the pattern of FLT3/D835 mutations in initial and relapsed AML were observed. Our results indicate an association of FLT3/ITD with the adverse outcome in AML patients treated with standard induction chemotherapy. Because FLT3/ITD mutation is a target for specific therapeutic inhibition, its early detection could be helpful in clinical practice.

Clinical stage-depending decrease of NK cell activity in multiple myeloma patients.

Natural killer cells, as an important subpopulation of cells of the innate immune system have an essential role in defense of the rise and spread of malignancy. These cells have a CD3-CD16 + CD56+ phenotype and they are functionally defined by their ability to lyses tumor cells. We here show that decrease of NK cell activity was significantly associated with advanced clinical stage, increased lactate dehydrogenase (LDH), percentage infiltration of bone marrow with plasma cells, and beta-2 microglobulin. The patients with higher NK cell activity at presentation after receiving VAD protocol have better cumulative survival in comparison with those with low NK cell activity.

Outcomes of primary thyroid non-Hodgkin's lymphoma: a series of nine consecutive cases.

Primary non-Hodgkin's lymphoma (NHL) of the thyroid gland is a rare disease with an incidence of 0.5 per 100,000 population. Stages IE and IIE thyroid NHL have been traditionally treated by surgical resection; however, modern treatment consists of chemotherapy and local radiotherapy, and surgery is often reserved for tissue diagnosis and relief of airway compression. We retrospectively reviewed the management and outcomes of nine consecutive patients with thyroid NHL, eight females and one male (median age 63 yr, range 34-71 yr) treated between 1994 and 1999. Five patients had disease stage IE and 4 stage IIE. Median follow-up was 72 mo. Pathohistology and immunohistochemistry identified two patients with mucosa-associated lymphoid tissue (MALT), three follicular center cell lymphoma (FCC), two patients large B-cell lymphoma (BLCL), one a marginal zone lymphoma (MZL), and one patient a peripheral T-cell lymphoma (PTCL). Total thyroidectomy was performed in three patients and subtotal thyroidectomy in four. One (MALT) patient underwent surgery alone; three patients surgery, radiotherapy, and chemotherapy (two FCC, one PTCL); three patients surgery and chemotherapy (one MALT, one FCC, one LBCL); and two chemotherapy alone (one LBCL, one MZL). Median survival was 79 mo (range 13-124 mo). The PTCL patient, a 34-yr-old man, died from disseminated disease at 13 mo despite secondary chemotherapy, and one LBCL patient with extensively invasive local disease died from stroke 17 mo after diagnosis. The remaining seven patients remain in remission with no local or systemic relapse at a mean of 86 mo. With appropriate therapy primary thyroid NHL has a favorable course; however, prognosis depends on the histology, local spread, and the stage of the disease at presentation, as well as the patient's performance status. Surgery in combination with chemotherapy and/or radiotherapy is still warranted for intermediate and high-grade thyroid NHLs, with over 77% of patients achieving long-term remission. Peripheral T-cell lymphoma carries a poor prognosis.

A rare case of enteropathy-associated T-cell lymphoma presenting as acute renal failure.

Enteropathy-associated T-cell lymphoma (EATCL) is a high grade, pleomorphic peripheral T-cell lymphoma usually with cytotoxic phenotypes. We describe a first case of patient with EATCL that is remarkable for its fulminant course and invasion of both kidneys manifested as acute renal failure. The patient was a 23 year old woman with a long history of celiac disease. She was presented with acute renal failure and enlarged mononuclear infiltrated kidneys. Diagnosis of tubulointerstitial nephritis and polyserositis was confirmed with consecutive pulse doses of steroid therapy. After recovery, she had disseminated disease two months later. Magnetic resonance imaging showed thickened intestine wall, extremely augmented kidneys, enlarged intra-abdominal lymph nodes with extra-luminal compression of common bile duct. Laparotomy with mesenterial adipous tissue and lymph glands biopsy was done. Consecutive pathophysiological and immunohistochemical analyses confirmed the diagnosis of EATCL: CD45RO+, CD43+, CD3+. The revision of renal pathophysiology substantiated the diagnosis. The patient received chemotherapy, but unfortunately she died manifesting signs of pulmonary embolism caused by tumor cells.

FLT3/D835 mutation and inversion of chromosome 16 in leukemic transformation of myelofibrosis.

We present an atypical case of myelofibrosis developing into secondary leukemia FAB subtype M4, with inversion of chromosome 16, FLT3/D835 point mutation and diffuse osteolytic lesions accompanied by elevated TNF-alpha. The simultaneous occurrence of these mutations reflects the progressive association of genetic lesions developing into secondary leukemia with a relatively benign course.

Changes in prothrombin and activated partial thromboplastin time during replacement therapy with human recombinant growth hormone in growth hormone deficient adults.

BACKGROUND: In rodents, Growth Hormone (GH) has been shown to stimulate coagulation parameters, including Prothrombin Time (PT), activated Partial Thromboplastin Time (aPTT) and vitamin K dependent coagulation factors. However, there are no reports on the influence of GH replacement therapy on global coagulation tests in Growth Hormone Deficiency (GHD). OBJECTIVE: The aim of this study was to investigate the effects of GH administration on basic coagulation parameters: PT, aPTT and fibrinogen concentrations in adult GHD patients before and during one year of GH replacement. DESIGN: Twenty-one adult patients with severe GHD (mean age +/- SE: 38.6 +/- 2.8 years) were included in this hospital based, prospective, interventional study. All patients were treated with rhGH for 12 months (GH dose: 0.4 mg/day for male and 0.6 mg/day for female patients). IGF-1 concentrations were determined using RIA-INEP kits. Basic coagulation tests, i.e. aPTT and fibrinogen concentrations, were measured before and after 3, 6 and 12 months of treatment with rhGH. Control values were obtained from fourteen "healthy" subjects matched by age, sex and body mass index (BMI). RESULTS: At baseline, we observed no significant differences in PT, aPTT and fibrinogen values between GHD and healthy subjects. IGF-1 concentrations increased significantly within 3 months of GH therapy (8.2 +/- 1.5 vs. 24.2 +/- 2.9 nmol/l, p <0.05) and remained stable thereafter. A significant increase in PT values, which was more pronounced in female subjects, was noted after 6 and 12 months of treatment with GH. aPTT values increased significantly after 12 months of treatment only in male patients (28.8 +/- 4.6 vs. 39.7 +/- 2.1 s.; p <0.05). No significant changes in fibrinogen concentrations were found during the study. CONCLUSIONS: Twelve months of GH replacement therapy led to a significant increase in PT and aPTT values in adult GHD patients, while fibrinogen concentrations did not change. Changes in PT were more pronounced in female GHD patients, while an increase in aPTT values was observed only in male patients with GHD. The clinical significance of these changes needs further evaluation.

MUM-1 and bcl-2 Positive Primary Diffuse Large B Cell Non-Hodgkin's Lymphoma of the Colon.

Primary diffuse large B cell lymphoma (DLBCL) presents as a nodal and extranodal disease. The most common extranodal site is the gastrointestinal tract (GI), with the stomach most frequently involved, followed by the small bowel. Primary DLBCL of the large bowel accounts for 0.2%-1.2% of all colonic tumors. We present two patients who underwent radical resections of right colonic tumors. They were diagnosed with primary colonic DLBCL following histological and immunohistochemical testing of the excised tissues, and were determined as being in stage IIE of the disease. The tumors expressed CD20 markers. Both received multi-agent chemotherapy with combined immunotherapy and remain in complete remission at 4 and 5 years.

Decreased CD161 activating and increased CD158a inhibitory receptor expression on NK cells underlies impaired NK cell cytotoxicity in patients with multiple myeloma.

AIM: As innate immune cells natural killer (NK), NK-like T and CTLγδ are important in antitumour response in multiple myeloma (MM), the aim of this study was to investigate some functional and phenotypical characteristics of these cells in MM. METHODS: 29 patients with MM prior to therapy, in clinical stage I-III and 15 healthy controls (HCs) were investigated. Percent of immune cells in peripheral blood, NK cell activity, expression of activating (CD161) and inhibitory (CD158a, CD158b) NK cell receptors on CD3-CD16+ NK cells were evaluated using 51-chromium-release assay and by flow cytometry. Production of interleukin (IL) 2 and tumour necrosis factor (TNF)α was analysed in supernatants from in vitro activated peripheral blood mononuclear cells. RESULTS: In patients with MM the percent of NK cells and their two subsets did not differ from controls, while NK-like T and CTLγδ cells were significantly decreased. Significant impairment of NK cell cytotoxicity, CD107a expression and interferon γ intracellular level was also shown. There was a significant decrease in CD161 and an increase in CD158a receptor expression on NK cells in these patients. Also IL-2 production was lowest in clinical stage III. However, TNF-α production did not differ between patients and HCs. CONCLUSIONS: Altered expression of CD161 activating and CD158a KIR inhibitory receptor is responsible for impaired antitumour activity of NK cells in MM patients. These new biomarkers may be helpful for patient selection for immunotherapy with cytokines, and novel KIR blocking monoclonal antibodies that enhance NK cell antimyeloma activity and provide clinical benefit.

Association of Bax Expression and Bcl2/Bax Ratio with Clinical and Molecular Prognostic Markers in Chronic Lymphocytic Leukemia.

BACKGROUND: In chronic lymphocytic leukemia (CLL), in vivo apoptotic resistance of malignant B lymphocytes results, in part, from the intrinsic defects of their apoptotic machinery. These include genetic alterations and aberrant expression of many apoptosis regulators, among which the Bcl2 family members play a central role. AIM: The aim of this study was to investigate the association of pro-apoptotic Bax gene expression and Bcl2/Bax ratio with the clinical features of CLL patients as well as with molecular prognostic markers, namely the mutational status of rearranged immunoglobulin heavy variable (IGHV) genes and lipoprotein lipase (LPL) gene expression. METHODS: We analyzed the expression of Bax mRNA and Bcl2/Bax mRNA ratio in the peripheral blood mononuclear cells of 58 unselected CLL patients and 10 healthy controls by the quantitative reverse-transcriptase polymerase chain reaction. RESULTS: We detected significant Bax gene overexpression in CLL samples compared to non-leukemic samples (p=0.003), as well as an elevated Bcl2/Bax ratio (p=<0.001). Regarding the association with prognostic markers, the Bcl2/Bax ratio showed a negative correlation to lymphocyte doubling time (r=-0.307; p=0.0451), while high-level Bax expression was associated with LPL-positive status (p=0.035). Both the expression of Bax and Bcl2/Bax ratio were higher in patients with unmutated vs. mutated IGHV rearrangements, but this difference did not reach statistical significance. CONCLUSIONS: Our results suggest that dysregulated expression of Bcl2 and Bax, which leads to a high Bcl2/Bax ratio in leukemic cells, contributes to the pathogenesis and clinical course of CLL.

A der(14)t(1;14)(q12;p11) in chronic myelomonocytic leukemia.

Duplication of the long arm of chromosome 1 (1q) is widely reported in human neoplasia, including the myelodysplastic syndromes (MDS). So far, it has not been described as a single aberration in the chronic myelomonocytic leukemia (CMML), a subtype of MDS. Rather, trisomy 1q was always a part of complex chromosome changes affecting the subtypes of MDS other than CMML. We report on a patient with CMML with an unbalanced translocation of the entire 1q onto the short arm of chromosome 14 as a sole cytogenetic abnormality. Fluorescence in situ hybridization (FISH) analysis with an alpha-satellite probe for the paracentric region of the long arm of chromosome 1 confirmed the presence of trisomy 1q in a derivative chromosome, der(14)t(1;14)(q12;p11). The discrepant results between the metaphase cytogenetics (100% abnormal) and interphase cytogenetic (71% nuclei with 3 signals) suggest that trisomy 1q, even in the absence of additional cytogenetic changes, has a sufficient leukemogenic potential to confer a proliferative advantage on hematopoietic cells committed to monocyte stemline both in vitro and in vivo. The literature data on partial and complete trisomy 1q in CMML is reviewed.