Fatal complication of sickle cell anemia in an immigrant patient rescued from the mediterranean sea.

The aim of this case report is to share with the forensic science community the experience of a rare complication of sickle cell anemia: acute chest syndrome. In October 2016, at the port of the city of Trapani (Sicily, Italy), the landing of an ONG "Médecins Sans Frontières" ship took place with 548 non-EU citizens and a corpse on board. The man, in the hours before his death, complained of severe chest pain and respiratory difficulties, and, despite of the therapeutic aids and resuscitation maneuvers, lastly died. The Public Prosecutor ordered that autopsy be executed on the corpse of the young Ghanaian, and it was to be supplemented by histological, toxicological, genetic investigations, and the dating of the biological age. The autoptic examination findings were indicative of bilateral bronchopneumonia, and were also confirmed by the histological findings, which identified a condition of massive adipose pulmonary embolism, due to the presence of extramedullary hematopoietic tissue, site of endovascular thrombosis secondary to hemolysis of sickle cells. The spleen appeared of small volume, with fibrotic phenomena. The predisposition to infections, thrombosis, extramedullary hematopoiesis are all complications of sickle cell anemia. The severe pulmonary condition characterized by vaso-occlusive findings and pulmonary inflammation with infiltrate, symptoms like fever, chest pain and severe systemic hypoxia allowed to ascribe the plausible cause of death as acute chest syndrome, a rare complication of sickle cell anemia. The peculiarity of this clinical case is also related to the methods of medical intervention (boat with non-governmental medical support for assistance to migrants).

Idiopathic ventricular arrhythmia in a young man: a case report.

Ventricular ectopics can potentially lead to ventricular fibrillation (VF). A case of idiopathic VF that began as ventricular bigeminy is presented. A 30-year-old man lost consciousness transiently while driving but made a complete recovery soon after. He was pale and sweaty at the onset of the event. There was neither a history of ill health nor a family history of sudden cardiac death. He was asymptomatic on arrival at the emergency department (ED) with sinus tachycardia. Two hours later ventricular bigeminy was observed. This subtle presentation did not qualify him for being high risk according to the American College of Physician's recommendations or the San Francisco syncope rule, which almost led to his discharge from the ED. Despite this, he was admitted for observation. The patient had four VF arrests overnight, which were eventually terminated by emergency radiofrequency ablation. Upon further investigation, he was found to be normal on cardiac magnetic resonance imaging, echocardiogram and 24-h Holter monitoring. His serum biochemistry was normal, ruling out electrolyte disturbances. He eventually received an implantable cardioverter and remained free of recurrences in the subsequent months. This case serves as a reminder not to ignore ventricular ectopics or bigeminy.

Utility of post mortem computed tomography in clivus fracture diagnosis. Case illustration and literature review.

Clivus fractures are usually associated with head blunt trauma due to traffic accident and falls. A 23 - year-old man died immediately after a smash-up while he was stopping on his motorcycle. Post-mortem Computed tomography (PMCT), performed before autopsy, revealed a complex basilar skull base fractures associated with brainstem and cranio-vertebral junction injuries, improving the diagnostic performance of conventional autopsy. Imaging data were re-assessable and PMCT offers the possibility to perform multiplanar and volume rendered reconstructions, increasing forensic medicine knowledge related to traumatic injuries.

All-trans retinoic acid and low-dose cytosine arabinoside for the treatment of 'poor prognosis' acute myeloid leukemia.

Thirty-three patients with 'poor prognosis' acute myeloid leukemia, no longer suitable for aggressive chemotherapy, were treated with daily oral all-trans retinoic acid (45 mg/m2) daily and subcutaneous cytosine arabinoside (20 mg standard dose twice a day, day 1 to 10, every 4 weeks). Seventeen patients were males and 16 females, the median age was 67 (range 39-82 years). Eleven patients were at onset of disease, 15 were refractory to previous conventional therapies, three were in first relapse and three in second relapse and one patient had a secondary AML. Seventeen patients had a bone marrow blast infiltration < 50% and 16 > or = 50%. A total of 16 (48%) patients entered complete remission; the rate of complete remission increased to 88% in those patients (n = 17) with < 50% blast infiltration at the time of entering the study. Seventeen patients (52%) were resistant. The difference in response to therapy, according to bone marrow blast percentage (< or > or = 50%), was statistically significant (P < 0.001). Median duration of complete remission was 34.4 weeks (range 6.4-62.8). Mild to moderate hematologic toxicity was the most common side-effect. In conclusion all-trans retinoic acid and low-dose cytosine arabinoside appears to be an effective regimen for inducing complete remission in 'poor prognosis' acute myeloid leukemia and patients with < 50% bone marrow infiltration are likely to represent the ideal target to receive this combination therapy.

Prognostic value of cell marker analysis in de novo acute myeloid leukemia.

Clinical and cytologic characteristics were correlated to immunologic markers in 154 patients with newly diagnosed acute myeloid leukemia (AML). The panel of monoclonal antibodies (MoAbs) was selected to identify differentiation-associated antigens of both the myeloid and the lymphoid lineages (CD13, CD33, CD14, CD15, CD7, CD34, CD10, HLA-DR, CD19, CD2, CD5, TdT). The expression of multidrug resistance P-glycoprotein (P-170) was also evaluated in 117 patients. Differences in antigenic expression was observed among the various French-American-British (FAB) subgroups. HLA-DR was poorly expressed on the blasts of acute promyelocytic leukemia (M3), and was always found in FAB M5. CD34 was detectable in all M0 cases and only in one M3 (p < 0.001). Lymphoid-associated antigens were positive in 74 cases (48.1%). In particular, CD7 was found in 49 patients (31.8%), and TdT in 30 (21.3%), 15 samples displaying coexpression of these two antigens. The incidence of CD7+ cases was particularly elevated in M0 and M5 AML (p = 0.005). It significantly correlated with the expression of CD34, HLA-DR, P-170 (p < 0.001, p = 0.018 and p = 0.034 respectively), and with a leukocyte count > 50 x 10(9)/l (p = 0.038). Sixty-nine (59%) samples demonstrated P-170 positivity. Again, this phenotype was particularly expressed in the poorly differentiated forms (M5, M0 and M1) and showed significant correlation with the immaturity markers CD34, CD7 and HLA-DR (p = 0.013, p = 0.022 and p = 0.001, respectively). Expression of individual antigens correlated with prognosis. Refractoriness to first line therapy was associated with CD7 expression (p = 0.002) and P-170 (p = 0.001). The CD7 marker was also significantly associated with a very low overall survival (p < 0.001) and continuous complete remission (p < 0.001). CD14 expression also significantly predicted lower survival rates (p = 0.033). The combination (CD7+ CD14+) identified a subset of patients with a particularly adverse outcome. The prognostic value of CD7 expression, alone or in combination with other markers, was confirmed in multivariate analysis.

Prognostic relevance of the expression of Tdt and CD7 in 335 cases of acute myeloid leukemia.

We have analyzed the expression of Tdt and CD7 in 335 cases of unequivocal acute myeloid leukemia (AML). Tdt was expressed in 80 (25%) of 321 evaluable cases. Twenty-six of 77 (34%) Tdt+ patients assessable for response, entered complete remission (CR) vs 121 of 209 (58%) Tdt- cases (P < 0.001). CD7 was expressed in 102 of 332 (30%) evaluable cases; 37 of 93 assessable (40%) CD7+ patients attained a CR as compared to 114/204 (56%) CD7- (P = 0.013). Duration of survival was significantly shorter for patients with CD7+ or Tdt+ AML (P = 0.006 and 0.001, respectively). In a multivariate analysis, Tdt was found to significantly adverse achievement of CR (P = 0.018), while CD7 affected duration of CR (P = 0.037). Overall the expression of either Tdt or CD7 correlated with a relatively high expression of CD34 (P < 0.001), GP-170 (P = 0.003), lymphoid antigens (LyAg) (P < 0.001), t(9;22) or anomalies of chromosome 5/7 (P < 0.001). Finally, we pooled the patients into four phenotypic classes, according to the presence of Tdt, CD7 or both: [Tdt-CD7-], [Tdt+CD7-], [Tdt-CD7+] and [Tdt+CD7+]. The category [Tdt+CD7+] was characterized by a more unfavorable outcome as suggested by a lower rate of CR (P < 0.001) and a shorter duration of survival as compared to cases [Tdt-CD7-], [Tdt+CD7-] and [Tdt-CD7+] (P = 0.002). This figure is consistent with the frequent convergence in the subset [Tdt+CD7+] of GP-170 positivity (P = 0.003), translocation t(9;22), anomalies of chromosome 5 and/or 7 (P < 0.001) and signs of lineage infidelity (deviant expression of lymphoid antigens) (P < 0.001). We conclude that the expression of Tdt or CD7 is associated with an unfavorable outcome and that the combination of both defines a clinical subset with a poorer prognosis due to the significantly higher association with MDR phenotype, and 'poor prognostic' chromosomal abnormalities.

High-dose chemotherapy in adult acute myeloid leukemia: rationale and results.

Preclinical studies and retrospective evaluations of clinical trials of a number of cytotoxic drugs have provided a rationale for the use of high doses of chemotherapy in adults with acute myeloid leukemia (AML). To maximize cure and remission rates at an acceptable cost in toxicity, many schedules and combinations of dose-intensive chemotherapy have been tested in recent years in patients with de novo disease, cytosine arabinoside (Ara-C) being the most extensively evaluated drug. In this article we review the principal results of both randomized and non-controlled studies. Our analysis indicates that high-dose Ara-C (HIDAC) used during induction results is no substantial benefit relative to conventional doses of drug. On the other hand, consolidation with HIDAC is a major advance in the treatment of this disease. In fact, in individuals less than 60 years of age and a favorable or intermediate-risk karyotype, HIDAC-based regimens have resulted in survival estimates comparable to those of autologous or allogeneic bone marrow transplantation. Yet, the role of HIDAC is irrelevant in younger individuals with an unfavorable cytogenetic pattern and detrimental in patients greater than 60 years of age. Since recently new cytotoxic agents have expanded the armamentarium of antileukemic drugs, well conducted randomized trials of dose intensive chemotherapy still need to be performed to optimize schedules and combinations of drugs in patients with AML.

A microgranular variant of acute promyelocytic leukemia with atypical morpho-cytochemical features and an early myeloid immunophenotype.

This report describes a unique case of acute promyelocytic leukemia (APL) showing elusive morphologic features, an atypical pattern of cytochemical reactions, and a previously unreported immunophenotype consistent with a very early myeloid form: CD13 (+), CD33 (+), CD9 (+), CD2 (+), HLA-DR (-), CD34 (+), CD117 (+), and TdT (+). The diagnosis of AML M3 variant was made only after genotypic analyses revealed the PML/RAR alpha rearrangement associated with the typical (15;17) (q22;q21) translocation. This example of 'asynchronous differentiation' emphasizes the need for a multiparameter approach to the diagnosis of acute leukemia.

P-glycoprotein and terminal transferase expression identify prognostic subsets within cytogenetic risk classes in acute myeloid leukemia.

Clinical and biological features were assessed in 204 consecutive de novo adult acute myeloid leukemia (AML) patients who received intensive chemotherapy regimens. Multiparameter flow cytometric assays both of the multidrug resistance (MDR-1)-associated P-glycoprotein (PGP) using the UIC2 monoclonal antibody (MoAb), and of terminal transferase (TdT) were performed. Cytogenetic findings were obtained from 196 patients with high resolution banding. At onset, UIC2 and TdT positivities were detected in 58.5% and 24% of cases, respectively. There were strict correlations either between UIC2 negativity and FAB M3 or between TdT and FAB M0-M1 (P = 0.001 and < 0.0001, respectively). On the other hand, age was significantly associated with cytogenetic risk classes (P < 0.0001). CD34 positivity was highly correlated with TdT expression (P < 0.0001). Moreover, CD7 and CD11b were significantly represented in UIC2+ subset (P < 0.0001). Rhodamine 123 (Rh 123) efflux was significantly higher in 75 UIC2 positive patients compared to 65 UIC2 negative ones (P < 0.001). As regards to cytogenetics, TdT positivity was strongly related either to t(9;22) or single/associated anomalies of chromosome 7; on the other hand, most or all cases with t(8;21) or t(15;17) were UIC2 or TdT negative, respectively. The rate of first complete remission (CR) differed both between UIC2+ and UIC2- cases and between TdT+ and TdT- ones (40% versus 72%, P < 0.001; and 36% versus 61%, P = 0.001, respectively). The survival rates (Kaplan-Meier method) were significantly shorter either in UIC2+ or in TdT+ patients (P = 0.005 and = 0.011, respectively). UIC2 and TdT negative cases showed longer remission duration (P = 0.03 and = 0.22, respectively). The additional effect of UIC2 and TdT on prognosis allowed us to identify two subsets of patients, the first [UIC2- TdT-] at better and the second [UIC2+ TdT+] at worse clinical outcome compared to single UIC2 and TdT cases, concerning CR (P < 0.001), survival (P < 0.0001) and CR duration (P = 0.007). The combinations [UIC2+ TdT-] and [UIC2- TdT+] showed an intermediate clinical course. A strong difference was found between poor risk and intermediate/favorable risk cytogenetic classes with regard to CR rate (P < 0.0001), overall survival and CR duration (P < 0.001). Nevertheless, within the poor risk class, UIC2 positivity was able to identify patients at worst prognosis with regard to CR (P = 0.005), survival (P = 0.02) and CR duration (P = 0.015). On the other hand, UIC2 and TdT negativity allowed us to distinguish patients with longer survival (P = 0.012 and = 0.04, respectively) and CR duration (P = 0.04 and = 0.025, respectively) within the intermediate/favorable risk class. The independent prognostic value of UIC2, TdT and cytogenetic risk classes was confirmed in multivariate analysis. These results suggest that PGP and TdT expressions, together with cytogenetic findings, may represent a basic predictor of chemotherapeutic failure in AML.

A comparative analysis of FISH, RT-PCR, and cytogenetics for the diagnosis of bcr-abl-positive leukemias.

Philadelphia (Ph) chromosome-positive leukemias, with the bcr-abl gene translocation, have a dismal prognosis. The identification of Ph-positive patients is vitally important because only aggressive therapeutic approaches, such as allogeneic bone marrow transplantation, may result in long-term disease-free survival. Routine diagnostic methods, such as Southern blot analysis and cytogenetics, may lead to false-negative results. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis is considered the most sensitive tool for the detection of the bcr-abl translocation, and it is widely used alone or in combination with karyotyping or Southern blot analysis to identify Ph-positive cases. In this study, we used fluorescence in situ hybridization (FISH) with BCR and ABL double-color probes for detecting Ph-positive leukemias. The FISH results were compared with the results of cytogenetic and RT-PCR analyses in 75 patients with leukemia or other myeloproliferative syndromes (chronic myeloid leukemia, 30; acute lymphoblastic leukemia, 24; acute myelogenous leukemia, 6; essential (hemorrhagic) thrombocythemia, 12; chronic myelomonocytic leukemia, 2; and polycythemia vera, 1). FISH analysis proved to be simple, extremely reliable and sensitive; bcr-abl fusion detection was successful in the presence of all types of molecular junctions i.e., (b2a2, b3a2, and e1a2). Furthermore, a Ph-positive case that proved fusion negative by RT-PCR was identified as positive by FISH. The sensitivity of RT-PCR and FISH related to Ph-positive cases were 97% and 100%, respectively. Regarding specificity, in 4 (5%) of 75 patients, RT-PCR provided false-positive results. Cross-contamination was identified because a new specimen was harvested and reanalyzed when FISH, cytogenetics, and RT-PCR results were contradictory. We believe FISH is an optimal diagnostic method to detect bcr-abl translocation that can be used alone or to validate the results of RT-PCR analysis.

CD7 expression in acute myeloid leukemia.

The clinical significance of the expression of CD7 antigen on the blasts of 207 consecutive patients with de novo acute myeloid leukemia (AML) was evaluated. For this purpose, fifty-three CD7+ patients (23 females and 30 males; mean age 52 years) were analyzed and classified into the following subtypes according to French-American-British (FAB) classification: 7 M0, 13 M1, 9 M2, 1 M3, 9 M4, 14 M5. Immunophenotypic studies were carried out by flow cytometry and blast cells were selected on the basis of forward light scatter gating and pan-myeloid marker, either CD13 or CD33. All the CD7+ patients were negative for surface CD3 and T-cell-receptor (TCR) molecules. We found no correlation between CD7 expression and sex, age, hepatosplenomegaly and/or central nervous system involvement. The immaturity of CD7+ leukemic cells was supported by the high expression of CD34 (P = 0.001). CD7 positivity was significantly associated with a white blood cell count (WBC) greater than 100 x 10(9)/L (P = 0.003). P-Glycoprotein (P-170) expression was also evaluated in 135 patients by a flow-cytometric assay: there was a close relationship between CD7 and P-170 positivity (P < 0.001). For remission induction, all patients received therapeutic regimens routinely used for AML. The complete remission (CR) rate was significantly lower in CD7+ cases (32% vs 74%, P = 0.001). The overall survival and disease free survival rate of CD7+ AML was lower than those of CD7- patients (P < 0.001 and = 0.002, respectively). CD7+ AML with coexpression of CD14 had a particularly unfavourable response and prognosis in comparison with CD7+ patients without CD14.(ABSTRACT TRUNCATED AT 250 WORDS)

P-glycoprotein expression in de novo acute myeloid leukemia.

Detection of the multidrug resistance P-glycoprotein (PGP) phenotype was performed at the time of diagnosis in 223 patients with acute myeloid leukemia (AML) by flow cytometry using C219 Monoclonal Antibody (MoAb). On the other hand, JSB1 MoAb was tested in 173 of these samples. At onset, PGP was detected in 57.4% of cases with C219 and 75.9% of cases with JSB1. There was no correlation between PGP expression and sex, age, marrow blast percentage or extramedullary disease. On the contrary, strict correlations were noted either between C219 negativity and FAB M3 subtype or between C219 positivity and FAB M5 group (P = 0.003). Significant correlation was found between PGP phenotype and CD7, as 143 of 223 samples had similar patterns of staining with C219 (P < 0.0001). Finally, there was a close relationship between C219 and JSB1 positivity: all the C219+ cases were positive for JSB1 (P < 0.0001). Concerning the karyotype, most patients with monosomy or del (7) were MDR positive; on the other hand, most patients with t(8;21) or t(15;17) were MDR negative. Rh123 accumulation studies showed a significant decrease of mean fluorescence intensities both in C219 and in JSB1 positive cases in comparison with PGP negative ones (P < 0.001). A significant decrease of remission induction rates (CR) was highlighted both between C219+ and C219- and between JSB1+ and JSB1- cases (32.1% v 62.1% and 32.6% v 73.8%, respectively, with P < 0.0001). The overall survival and the remission duration (CCR) were significantly shorter both in C219+ and in JSB1+ patients with no relationship to age. Furthermore, a higher rate of early relapses was noted among MDR+ when compared with MDR- patients both for C219+ and JSB1+ cases. The combination (C219- JSB1+) identified a subset of patients with an intermediate prognosis. On multivariate analysis, C219 and JSB1 were confirmed to be independent prognostic factors for achievement of CR, overall survival and CCR. In conclusion, the assessment of MDR phenotype by flow cytometry is a crucial prognostic factor of treatment outcome in AML.

Simultaneous occurrence of monoclonal gammopathy and acute secondary leukemia with overexpression of P-glycoprotein.

A 52-year-old woman, previously treated with chemo- and radiotherapy for Hodgkin's disease, developed an acute non-lymphoid leukemia and, contemporarily, an IgG-kappa paraproteinemia. Cytogenetic analysis showed a major clone, representing 90% of observed metaphases, with monosomy of chromosomes 5 and 14. In addition, leukemic cells exhibited a high expression of the P-glycoprotein, a transmembrane glycoprotein involved in the multidrug-resistance mechanism. Possible explanations for this cluster of findings are provided.

Investigating the changes in extreme rainfall series recorded in an urbanised area.

The aim of this study is to investigate and quantify changes in the rainfall regime of the metropolitan area of Palermo characterised by increasingly strong urbanisation. The rainfall data, considered in this study, were collected on a yearly basis from eight rain gauges within and outside the metropolitan area of Palermo, Sicily, Italy. A preliminary analysis made on the annual total rainfall depths showed a global reduction of total annual rainfall, with two different trends: more regular for the series observed in the rain gauges within the urbanised area and more variable for the series observed in the rain gauges outside the area. A further analysis has been performed using the series of maximum intensity for fixed duration (1, 3, 6, 12, 24 hrs) and annual daily maxima. The analysis of the trend in the extreme rainfall series has been performed by estimating the maximum rainfall depth corresponding to a fixed return period using the EV1 distribution with parameters estimated using L-moments. The analysis of all series indicates a global reduction of rainfall intensities, both for internal and external series, in disagreement with the results obtained by other authors.

[Therapeutic strategy in thymomas]. / Strategia terapeutica nei timomi.

Between July 1989 to February 1994 eight patients with thymoma were operated in the First surgical Clinic of University of Catania; in seven the neoplasia was associated with myasthenia gravis, the severity of which was evaluated according to the Osserman's classification. The surgical treatment has been: total thymectomy in four patients, in two total and partial resection was carried out respectively, and in two a macrobiopsy was performed. The postoperative staging was carried out according to Masaoka. The neoadjuvant chemotherapy and postoperative radiation therapy have been analyzed. The authors concluded that a rigorous anatomo-surgical and histopathological classification is the best way for the right use of postoperative adjuvant therapies to reduce the incidence of local and distant recurrence of these tumors.

[The surgical therapy of renal carcinomas. The prognostic factors and long-term results]. / Terapia chirurgica dei carcinomi renali. Fattori prognostici e risultati a distanza.

BACKGROUND: Image diagnosis of kidney neoplasms allows good preoperative staging using the TNM system, but surgical management cannot be based on these data because a tumour apparently confined to the kidney may have produced metastasis in extraregional lymph nodes. METHODS: Thirty-three patients with renal carcinoma were observed over a seven-year period. Preoperative staging using the TNM system was performed and then compared with postoperative staging. Radical nephrectomy and regional lymphadenectomy were performed in all patients. Extensive lymphadenectomy was undertaken in 10 cases presenting neoplasms larger than 10 cm. At the preoperative assessment, 20 patients were stage T2, 13 stage T3, for factor N six were N1, two M1; postoperative staging confirmed T2 in 15 cases, whereas five T2 became T3. After postoperative staging, the N1 patients increased from 6 to 13. Fifteen patients were at Robson's stage II, four at stage IIA, twelve IIIB and two stage IV. RESULTS: The 5-year survival rate was 63.2%. CONCLUSIONS: The authors conclude that from an analysis of the correlation between tumour size and lymph node metastasis it can be seen that low T values do not represent grounds for conservative treatment.

Distal pancreatectomy with en bloc resection of the celiac axis for pancreatic adenocarcinoma.

Resection of celiac axis for gastric cancer was first performed by Appleby in 1953. Subsequently, Mayumi et al. and Kimura et al. adopted this approach for locally advanced adenocarcinoma of pancreatic body. We are here describing this technique in case of adenocarcinoma of pancreatic body with infiltration of celiac axis achieving also gastric preservation. Our patient presented with diabetes, back pain and weight loss. CT scan showed a 3 cm mass in the body of pancreas infiltrating the origin of celiac axis, causing obstructive atrophy of pancreatic tail. Bilirubin, transaminases, amylase and tumoral markers were in the normal range with the exception of CEA (34 ng/ml) and chromogranin (30 IU/l). Vascular reconstruction imaging indicated the feasibility of the procedure. Under intraoperative ultrasound guidance we clamped the common hepatic artery in order to check the gastric and hepatic blood flow. We then performed a distal pancreasectomy and splenectomy with "en bloc" resection of celiac axis and regional lymphadenectomy. Appleby operation can increase the resectability of locally advanced cancer of the body and tail of the pancreas and offers not only a better life quality for patients but also perfect pain relief. This technique demands a multidisciplinary approach with careful pre and intra operative vascular evaluation, which is mandatory in assessing candidacy for this procedure.

In vitro down-regulation of bcl-2 expression by all-trans retinoic acid in AML blasts.

Using flow cytometry, we have investigated the effects of 0.5 microM all-trans-retinoic acid (ATRA) on bcl-2 expression in the blast cells of 25 acute myeloblastic leukemia (AML) patients and the HL-60 cell line after incubation for 6 days. We observed a significant decrease of bcl-2 expression after treatment with ATRA in 12 of 25 AML samples and the HL-60 cells. The mean fluorescence intensity (MFI) ratio for the bcl-2 levels of the ATRA responders (n = 12) was reduced to 7.9 +/- 4.8 following incubation with ATRA compared with 10.9 +/- 6.5 (mean +/- SD) for control samples incubated without ATRA (p = 0.011). There was no significant difference between the baseline bcl-2 MFI ratio in the ATRA responders (11.14 +/- 7, n = 12) and the non responders (14.18 +/- 11.3, n = 13; p = 0.432). The down-regulation of bcl-2 expression by ATRA was not significantly associated with CD34-negative or -positive AML. There was no correlation between AML subtypes and regulation of bcl-2 expression by ATRA. Complete remission and overall survival were not significantly improved in bcl-2 down-regulated cases. Our data confirm that ATRA can down-regulate the bcl-2 expression in AML blasts. Because many chemotherapeutic agents also operate through the activation of programmed cell death and bcl-2 levels are positively associated with resistance to apoptosis, ATRA can be used in combination chemotherapy to increase the chemosensitivity of some patients with AML.