Comparison of the accuracy of Monte Carlo and Ray Tracing dose calculation algorithms for multiple target brain treatments on CyberKnife.

Single plan multiple brain targets (MBT) stereotactic radiosurgery dose difference between Monte Carlo (MC) and Ray Tracing (RT) algorithms has not been studied. A retrospective study and dose measurements were performed to access factors influencing dose differences. Fifty-three RT treatment plans with a total of 209 brain metastases were extracted from Precision Treatment Planning System (TPS). These plans were generated using fixed cones and were delivered using the CyberKnife M6 system. The same treatment plans were recalculated using MC algorithm and keeping the beam parameters unchanged. MC calculated plan parameters were extracted and dose differences were normalised to MC calculated dose. Correlations were investigated. RT and MC calculated off-centre-ratio (OCR) and tissue-phantom-ratio (TPRs) were exported from the TPS and compared with measured. Plans with 5 gross tumour volumes (GTVs) were created on a phantom and dose measured using a CC04 ionisation chamber and microdiamond detector for comparison with calculated doses. Calculated and measured TPR agreed within ± 1% beyond depth of maximum dose. The OCR showed differences up to 4.3% in the penumbra and out-of-field (OOF) regions. Largest RT and MC calculated GTV mean dose difference was - 5.7%. An increase in the number of GTVs and reduction in the geometric separation of metastases were associated with increased differences between RT and MC calculated doses. In conclusion, calculated dose disagreement in MBT depends on the number of GTVs per plan, number of GTVs within a certain separation distance and plan complexity. MC dose calculation is recommended for complex CyberKnife SRS of MBT.

Intrafraction motion during CyberKnife® prostate SBRT: impact of imaging frequency and patient factors.

PURPOSE:  To determine the relationship between imaging frequencies and prostate motion during CyberKnife stereotactic body radiotherapy (SBRT) for prostate cancer. METHODS:  Intrafraction displacement data for 331 patients who received treatment with CyberKnife for prostate cancer were retrospectively analysed. Prostate positions were tracked with a large variation in imaging frequencies. The percent of treatment time that patients remained inside various motion thresholds for both real and simulated imaging frequencies was calculated. Results: 84,920 image acquisitions over 1635 fractions were analysed. Fiducial distance travelled between consecutive images were less than 2, 3, 5, and 10 mm for 92.4%, 94.4%, 96.2%, and 97.7% of all consecutive imaging pairs respectively. The percent of treatment time that patients received adequate geometric coverage increased with more frequent imaging intervals. No significant correlations between age, weight, height, BMI, rectal, bladder or prostate volumes and intrafraction prostate motion were observed. CONCLUSIONS: There are several combinations of imaging intervals and movement thresholds that may be suitable for consideration during treatment planning with respect to imaging and calculation of the margin between the clinical target volume and planning target volume (CTV-to-PTV), resulting in adequate geometric coverage for approximately 95% of treatment time. Rectal toxicities and treatment duration need to be considered when implementing combinations clinically.

A pregnant patient with schizophrenia - dilemmas of treatment and care. A problem still not only for psychiatrists. / Pacjentka ze schizofrenia w ciazy ­ dylematy leczenia i opieki. Problem nadal nie tylko dla lekarza psychiatry.

Pregnancy is a special period in any women's life. A pregnant woman who suffers from schizophrenia is a special patient and a huge challenge both for the psychiatrist and gynecologist. Such pregnancy is associated not only with the higher level of risk because of inappropriate diet, insufficient prenatal care and smoking but also because of the risk of possible mental degradation of a pregnant woman - occurrence or exacerbation of psychotic symptoms. Moreover, pharmaceutical treatment during pregnancy and its influence on fetus rises doubts and controversy. The aim of the study is to show three stories of pregnant patients treated for schizophrenia in a context of up to date knowledge on anti-psychotic treatment and to pay attention to the need of interdisciplinary approach to this special group of patients. Every pregnant woman suffering from schizophrenia requires individual approach in terms of treatment and care. The problem, which is still ignored, is the need of effective and constant cooperation between the doctors: a psychiatrist and a gynecologist since the very beginning of pregnancy, in order to assess the risk factors associated with pregnancy and periparturient period.

Calculation and measurement of doses in the surface layers of a phantom when using Tomotherapy.

BACKGROUND: The calculation and measurement on the surface of the skin presents a significant dosimetric problem because of numerous factors which have an influence on the dose distribution in this region. AIM: The overall aim of this study was to check the agreement between doses measured with thermoluminescent detectors (TLD) during tomotherapy photon beam irradiation of the skin area of a solid water cylindrical phantom with doses calculated with Hi-Art treatment planning system (TPS). MATERIAL AND METHOD: The measurements of the dose were made with the use of a solid water cylindrical phantom - Cheese Phantom. Two bolus phantoms were used: 5 mm and 10 mm Six different planning treatments were generated. The doses were measured using TL detectors. RESULTS: In the case of a tumor located near the surface of the skin, the mean dose for 0.5 cm bolus was - 1.94 Gy, and for 1 cm bolus - 2.03 Gy. For the tumor located inside the phantom and organ at risk on the same side that TL detectors, for a 0.5 cm bolus, mean dose was 0.658 Gy, and for a 1 cm bolus, 0.62 Gy. CONCLUSION: The analysis of results showed that the relative percentage difference between measured and planned dose in the field of irradiation was less than 10%, while the largest differences were on the board of the field of radiation and outside of the field of irradiation, where the dose was 0.08 Gy to 1 Gy.

Personalized radiotherapy treatment planning based on functional imaging.

In recent years, a huge progress in the field of radiotherapy could be observed. From treating patients with kilo-voltage X-rays units to cutting edge technology that can deliver a certain dose with an extreme precision. Modern radiotherapy is characterized, among others, by an individualized approach to the patient. This can be provided by functional imaging which is another step toward a better tumor control. In this paper, we discuss the potential application of functional imaging modalities in personalized radiotherapy planning with emphasis on dose painting. Some limitations of this approach will also be evaluated.

Comparison of dose distribution for head and neck cancer patients with and without dose painting escalation during radiotherapy realized with tomotherapy unit.

OBJECTIVE: To determine and quantify the percentage dose increase to organs at risk (OARs) with multiple-level dose painting (DP) for patients with head and neck cancer in comparison with standard regimen. METHODS: 12 patients who had undergone fluorine-18 fludeoxyglucose (18F-FDG) positron emission tomography (PET)/CT scan were retrospectively enrolled. Two treatment plans-one using DP escalation and one without-were optimized for each patient base on PET/CT data. The following variables were assessed: dose to OARs and target volumes; execution time; equivalent uniform dose; and normal tissue complication probability. RESULTS: No statistically significant differences in beam-on time were observed between plans with and without DP. However, significantly higher doses were observed for all DP-escalated plans in the OARs, with only two exceptions: the brain stem and V60Gy for the mandible. Multiple-level DP resulted in dose increases ranging from 3.0% to 12.9%, depending on the OAR. The largest increase was seen for the parotid glands and the smallest for the mandible. Significant differences in the equivalent uniform dose were observed only for the parotid glands and spinal column, where the dose without DP was lower. The normal tissue complication probability for most OARs was very small. CONCLUSION: Importantly, even though DP escalation resulted in higher doses to OARs vs conventional treatment planning, these usually did not exceed the dose tolerance levels. However, clinical trials are necessary to confirm the benefits of DP and to guarantee no additional toxicity. Advances in knowledge: Multiple-level DP by numbers resulted in 3.0-12.9% dose increase, depending on the OAR. Our findings may suggest that DP escalation to very high doses is feasible for about 83% of patients without higher toxicity; however, it still should be confirmed on a larger group of patients.

Carcinogenesis Induced by Low-dose Radiation.

BACKGROUND: Although the effects of high dose radiation on human cells and tissues are relatively well defined, there is no consensus regarding the effects of low and very low radiation doses on the organism. Ionizing radiation has been shown to induce gene mutations and chromosome aberrations which are known to be involved in the process of carcinogenesis. The induction of secondary cancers is a challenging long-term side effect in oncologic patients treated with radiation. Medical sources of radiation like intensity modulated radiotherapy used in cancer treatment and computed tomography used in diagnostics, deliver very low doses of radiation to large volumes of healthy tissue, which might contribute to increased cancer rates in long surviving patients and in the general population. Research shows that because of the phenomena characteristic for low dose radiation the risk of cancer induction from exposure of healthy tissues to low dose radiation can be greater than the risk calculated from linear no-threshold model. Epidemiological data collected from radiation workers and atomic bomb survivors confirms that exposure to low dose radiation can contribute to increased cancer risk and also that the risk might correlate with the age at exposure. CONCLUSIONS: Understanding the molecular mechanisms of response to low dose radiation is crucial for the proper evaluation of risks and benefits that stem from these exposures and should be considered in the radiotherapy treatment planning and in determining the allowed occupational exposures.

Inhibition of human glioma cell proliferation by altered Bax/Bcl-2-p53 expression and apoptosis induction by Rhaponticum carthamoides extracts from transformed and normal roots.

OBJECTIVE: The objective of this study was to determine the cytotoxic effect and apoptotic activity of Rhaponticum carthamoides transformed root (TR) and root of soil-grown plant (NR) extracts in a human glioma primary cells. The effect of these root extracts on cell cycle arrest, mitochondrial membrane potential (ΔΨm) and expression levels of apoptosis-related genes (Bcl-2, Bax and p53) were also examined. METHODS: Cytotoxic activity of root extracts was evaluated by MTT assay. Apoptosis and cell cycle were determined by flow cytometry. Expression levels of apoptosis-related gene were analysed by RT-PCR and Western blotting. ΔΨm was examined by the use of JC-1 reagent. KEY FINDINGS: Rhaponticum carthamoides root extracts inhibit cell growth and induce apoptosis in a dose-dependent manner in human glioma cells. The root extracts were found to up-regulate the pro-apoptotic Bax protein and down-regulate the anti-apoptotic Bcl-2 protein, consequently increasing the ratios of Bax/Bcl-2 protein levels. Moreover, an increase of the p53 protein level and reduction of ΔΨm in glioma cells were observed after treatment with NR and TR extracts. CONCLUSION: The results of this study may offer a new insight into the potential anticancer activity of R. carthamoides root extracts.

Comparison of treatment planning parameters for dose painting head and neck plans delivered with tomotherapy.

OBJECTIVE: The aim of this study was to determine which physical delivery parameter changes are most suitable for multiple-level dose-painting treatment plans with helical tomotherapy (HT). METHODS: A total of 96 treatment plans were generated for 12 patients who had undergone fluorine-18 fludeoxyglucose positron emission tomography/CT ((18)F-FDG-PET/CT) scan to plan head and neck cancer treatment. Based on these PET-CT images, the dose was escalated to 96 Gy in 32 fractions as a function of PET intensity values. The intensity-based prescription was converted into seven discrete dose levels. For the same patient, different HT plans were optimized by varying parameters such as field width (FW), pitch (PF) and modulation factor (MF). Dose conformity was evaluated using quality-volume histograms, quality factors (QFs), weighted index of achievement (IOAw), coldness (IOCw) and hotness (IOHw). Moreover, doses to organs at risk (OARs), target volumes and execution time were analyzed. RESULTS: Median QFs were the best for FW = 1.05 cm (QF = 2.10) and the worst for FW = 2.5 cm (QF = 3.04). The same trend was observed for IOAw, IOCw and IOHw. Combination of FW = 1.05 cm and MF = 5 leads to the longest beam-on time (above 25 min), whereas FW = 2.5 cm and MF = 3 lead to the shortest time (below 8 min). Data analyzed based on dose-volume histogram showed that changes in FW had the strongest impact on plan quality, whereas the effect of MF and PF changes was moderate. CONCLUSION: HT is suitable for multiple-level dose-painting treatment plans. ADVANCES IN KNOWLEDGE: Changes in FW and MF had the greatest impact on dose distribution quality and beam-on time. Changes in PF only influenced doses to the OARs.

A preliminary study of apoptosis induction in glioma cells via alteration of the Bax/Bcl-2-p53 axis by transformed and non-transformed root extracts of Leonurus sibiricus L.

Leonurus sibiricus L. is a traditional medicinal plant which occurs in southern Siberia, China, Korea, Japan, and Vietnam. The plant shows several pharmacological effects, but the most interesting is its anti-cancer activity. The aim of our study was to examine the induction of apoptosis in malignant glioma cells, the most aggressive primary brain tumors of the central nervous system, following treatment with transformed root (TR) or non-transformed root (NR) L. sibiricus extracts. Both the NR and TR extracts were found to have cytotoxic activity in the glioma primary cells. The human glioblastoma cell lines obtained from patients were confirmed to be tumorogenic by the following three markers: D10S1709, D10S1172, and D22S283. HPLC and MS analysis revealed the presence of polyphenolic compounds (chlorogenic acid, ferulic acid, caffeic acid, p-coumaric acid, ellagic acid, and verbascoside) in both sets of root extracts. In summary, our findings demonstrate that treatment of the glioma cells with NR and TR extracts resulted (a) in significant cell growth inhibition, (b) S- and G2/M-phase cell cycle arrest, and (c) apoptosis in a dose-dependent fashion by changing Bax/Bcl-2 ratio (about 4-fold increase) and p53 (5-fold increase) activation. These findings indicate that NR and TR extracts exhibit anti-cancer activity through the regulation of genes involved in apoptosis. This is the first report to demonstrate the cytotoxic effect of polyphenolic extracts from L. sibiricus roots against glioma cells, but further studies are required to understand the complete mechanism of its apoptosic activity.

Influence of the type of imaging on the delineation process during the treatment planning.

AIM: The aim of this study was to compare the intra- and interobserver contouring variability for structures with density of organ at risk in two types of tomography: kilovoltage computed tomography (KVCT) versus megavoltage computed tomography (MVCT). The intra- and interobserver differences were examined on both types of tomography for structures which simulate human tissue or organs. MATERIALS AND METHODS: Six structures with density of the liver, bone, trachea, lung, soft tissue and muscle were created and used. For the measurements, the special water phantom with all structures was designed. To evaluate interobserver variability, five observers delineated the structures in both types of computed tomography (CT). RESULTS: Intraobserver variability was in the range of 1-14% and was the largest for the liver. The observers segmented larger volumes on MVCT compared with KVCT for the trachea (79.56 ccm vs.74.91 ccm), lung (87.61 vs. 82.50), soft tissue (154.24 vs. 145.47) and muscle (164.01 vs. 157.89). For the liver (98.13 vs. 99.38) and bone (51.86 vs. 67.97), the volume on MVCT was smaller than KVCT. The statistically significant differences between observers were observed for structures with density of the liver, bone and soft tissue on KVCT and for the liver, lung and soft tissue on MVCT. For the structures with density of the trachea and muscles, there were no significant differences for both types of tomography. CONCLUSIONS: During the contouring process the interobserver and intraobserver contouring uncertainty was larger on MVCT, especially for structures with HU near 80, compared with KVCT.

Total skin electron beam (TSEB) therapy in pediatric patients: A review of the literature.

AIM: A literature review was undertaken to identify current TSEB therapy in pediatric patients. BACKGROUND: Total skin electron beam (TSEB) therapy is a method of irradiation with low energy electron beam dedicated to patients who have superficial skin lesions all over their body. Such skin malignancies are sparse among adults and even more uncommon with pediatric population. MATERIALS AND METHODS: In this study, all reported case reports were summed up with a special emphasis on techniques used, doses prescribed and special shielding of critical organs. Moreover, potential problems that were encountered during TSEB irradiation of very young patients were depicted. RESULTS: The literature has described only seven case reports of children undergoing TSEB therapy. Most of them were infants; however, two adolescents were also treated. For all infants, general anesthesia was provided to allow safe and accurate TSEB irradiation. The prescribed dose varied from 16 Gy to 28 Gy depending on the irradiation schedule and patient condition. Usually, boost fields were applied to the scalp and perineum. Typical shields for fingernails, toenails and lenses were usually used. CONCLUSION: This paper revealed that TSEB therapy may be considered as a palliative treatment for pediatric patients with leukemia cutis. However, its role is still unclear and should be further investigated.

Total skin electron irradiation techniques: a review.

Total skin electron irradiation (TSEI) has been employed as one of the methods of mycosis fungoides treatment since the mid-twentieth century. In order to improve the effects and limit the complications following radiotherapy, a number of varieties of the TSEI method, frequently differing in the implementation mode have been developed. The paper provides a systematic review of the different varieties of TSEI. The discussed differences concerned especially: (i) technological requirements and geometric conditions, (ii) the alignment of the patient, (iii) the number of treatment fields, and (iv) dose fractionation scheme.

Impact of the spinal cord position uncertainty on the dose received during head and neck helical tomotherapy.

INTRODUCTION: The study aims to establish the optimal planning risk volume (PRV) to the spinal cord (SC) for oropharyngeal cancer patients during adaptive radiation therapy with concurrent chemotherapy. METHODS: Geometrical uncertainties of the SC were evaluated. Differences between planned and delivered maximum doses to each part of the SC were established for every fraction dose and for cumulative dose. Maximum doses were evaluated as a dose received in 0.5 and 1 cm(3) of the analysed part of the SC defined as C1-C2, C3-C4, C5-C6 and C7-Th1 where Cn was a n-th cervical vertebra (n = 1, … , 7) and Th1 was the first thoracic vertebra. Finally, relations between dose differences and geometrical uncertainties were analysed using a relative risk (RR) and the importance of the PRV dose gradient to establish an optimal PRV for the SC. RESULTS: Prospective study based on the 875 observations from 25 oropharyngeal cancer patients was performed. The C1-C2 part of the SC is most exposed to risk of overdosage during chemoradiation for patients with oropharyngeal cancer due to its proximity to the clinical target volume (CTV). Doses received by other parts of the SC are smaller, with the lowest dose delivered to C7-Th1. For the C1-C2, delivered dose was higher than planned dose by 11%, while for the C7-Th1, this difference was smaller than 7%. The lowest movement of individual parts of the SC were detected for the C1-C2 and the highest for the C7-Th1. The standard deviations of the mean shift ranged respectively from 0.9 to 1.4 mm and from 1.3 to 2.9 mm. For each part of the SC delivered dose was smaller than planned dose to the PRV (RR < 1). CONCLUSION: Our study showed that for chemoradiation of oropharyngeal cancer, using daily image guidance and proper plan adaptation scheme, the current PRV margin for the SC could be reduced to 4 mm.

Empirical estimation of beam-on time for prostate cancer patients treated on Tomotherapy.

BACKGROUND AND AIM: This study proposed a method to estimate the beam-on time for prostate cancer patients treated on Tomotherapy when FW (field width), PF (pitch factor), modulation factor (MF) and treatment length (TL) were given. MATERIAL AND METHODS: THE STUDY WAS DIVIDED INTO TWO PARTS: building and verifying the model. To build a model, 160 treatment plans were created for 10 patients. The plans differed in combination of FW, PF and MF. For all plans a graph of beam-on time as a function of TL was created and a linear trend function was fitted. Equation for each trend line was determined and used in a correlation model. Finally, 62 plans verified the treatment time computation model - the real execution time was compared with our estimation and irradiation time calculated based on the equation provided by the manufacturer. RESULTS: A linear trend function was drawn and the coefficient of determination R (2) and the Pearson correlation coefficient r were calculated for each of the 8 trend lines corresponding to the adequate treatment plan. An equation to correct the model was determined to estimate more accurately the beam-on time for different MFs. From 62 verification treatment plans, only 5 disagreed by more than 60 s with the real time from the HT software. Whereas, for the equation provided by the manufacturer the discrepancy was observed in 16 cases. CONCLUSIONS: Our study showed that the model can well predict the treatment time for a given TL, MF, FW and it can be used in clinical practice.

Tomotherapy - a different way of dose delivery in radiotherapy.

AIM OF THE STUDY: Helical tomotherapy is one of the methods of radiotherapy. This method enables treatment implementation for a wide spectrum of clinical cases. The vast array of therapeutic uses of helical tomotherapy results directly from the method of dose delivery, which is significantly different from the classic method developed for conventional linear accelerators. The paper discusses the method of dose delivery by a tomotherapy machine. Moreover, an analysis and presentation of treatment plans was performed in order to show the therapeutic possibilities of the applied technology. Dose distributions were obtained for anaplastic medulloblastoma, multifocal metastases to brain, vulva cancer, tongue cancer, metastases to bones, and advanced skin cancer. Tomotherapy treatment plans were compared with conventional linear accelerator plans. RESULTS: Following the comparative analysis of tomotherapy and conventional linear accelerator plans, in each case we obtained the increase in dose distribution conformity manifested in greater homogeneity of doses in the radiation target area for anaplastic medulloblastoma, multifocal metastases to brain, vulva cancer, metastases to bones, and advanced skin cancer, and the reduction of doses in organs at risk (OAR) for anaplastic medulloblastoma, vulva cancer, tongue cancer, and advanced skin cancer. The time of treatment delivery in the case of a tomotherapy machine is comparable to the implementation of the plan prepared in intensity-modulated radiotherapy (IMRT) technique for a conventional linear accelerator. In the case of tomotherapy the application of a fractional dose was carried out in each case during one working period of the machine. For a conventional linear accelerator the total value of the fractional dose in the case of anaplastic medulloblastoma and metastases to bones was delivered using several treatment plans, for which a change of set-up was necessary during a fraction. CONCLUSION: The obtained results confirm that tomotherapy offers the possibility to obtain precise treatment plans together with the simplification of the therapeutic system.

[The psychometric properties of the Proverb-Metaphor Test]. / Wlasnosci psychometryczne Testu Przyslowie-Metafora.

UNLABELLED: Abstract thinking belongs to intellectual abilities of the highest level of the evolutionary development, thanks to which operations such a classification, systematisation and comparison are possible. AIM: An analysis of the psychometric properties of the Proverb-Metaphor Test (TPM) which has been used in the German speaking countries since 2001. The TPM was subject to the process of translation--retranslation--travesty in order to be adapted to clinical conditions in Poland. MATERIAL: 60 patients of the Department of Psychiatry, Medical University of Lublin with diagnosed paranoid schizophrenia (according to ICD-10 criteria). METHODS: PANSS and TPM was carried out amongst 15 patients at the beginning of the hospitalisation (the first stage of the research) and among all persons during the remission of syndromes (the second stage). The WAIS-R (PL) was used in the second stage. RESULTS AND CONCLUSION: 1. The TPM is a reliable instrument, of high criteria propriety. 2. The evaluated test is a relatively homogeneous research tool. 3. The TPM is, thanks to its simple construction and the short carrying out time, a practical method of abstract thinking evaluation. 4. The TPM may be a useful instrument enabling long term prognosis.

[The occurrence of psychotic disorders in epilepsy--a problem which is not fully known. Case history]. / Wystepowanie zaburzen psychotycznych w padaczce - problem nie do konca poznany. Opis przypadku.

Connections between mental disorders and epilepsy have been perceived for a long period of time. Despite numerous investigations into this problem, it still is not fully understood in regard to the fact that in epilepsy the psychoses are situated at the intersection of neurology and psychiatry and the same phenomena, if presenting the psychotic syndrome, are often described in different terms. The most serious diagnostic as well as therapeutic problems are psychotic disorders which coexist with epileptic seizures. The goal of this paper was to present the case history of a patient, who was diagnosed with a psychotic disorder caused by partial complex seizures. The patient presented was hospitalized many times and several different neuroleptic treatments were used unsuccessfully. During the course of the illness many severe episodes of psycho-motor agitation connected with auto-aggressive acts were observed. It was not until an EEG - Holter test was performed and antiepileptic drugs were added to the treatment which aided in making the correct diagnosis. This enabled the patient to return to his highest level of functioning since the onset of the illness.

The Src family kinase Hck couples BCR/ABL to STAT5 activation in myeloid leukemia cells.

Signal transducer and activator of transcription 5 (STAT5) is constitutively activated by BCR/ABL, the oncogenic tyrosine kinase responsible for chronic myelogenous leukemia. The mechanism of BCR/ABL-mediated STAT5 activation is unknown. We show here that the BCR/ABL SH3 and SH2 domains interact with hematopoietic cell kinase (Hck), leading to the stimulation of Hck catalytic activity. Active Hck phosphorylated STAT5B on Tyr699, which represents an essential step in STAT5B stimulation. Moreover, a kinase-dead Hck mutant and Hck inhibitor PP2 abrogated BCR/ABL-dependent activation of STAT5 and elevation of expression of STAT5 downstream effectors A1 and pim-1. These data identify a novel BCR/ABL-Hck-STAT5 signaling pathway, which plays an important role in BCR/ABL-mediated transformation of myeloid cells.

Complementary functions of the antiapoptotic protein A1 and serine/threonine kinase pim-1 in the BCR/ABL-mediated leukemogenesis.

BCR/ABL oncogenic tyrosine kinase activates STAT5, which plays an important role in leukemogenesis. The downstream effectors of the BCR/ABL-->STAT5 pathway remain poorly defined. We show here that expression of the antiapoptotic protein A1, a member of the Bcl-2 family, and the serine/threonine kinase pim-1 are enhanced by BCR/ABL. This up-regulation requires activation of STAT5 by the signaling from SH3+SH2 domains of BCR/ABL. Enhanced expression of A1 and pim-1 played a key role in the BCR/ABL-mediated cell protection from apoptosis. In addition, pim-1 promoted proliferation of the BCR/ABL-transformed cells. Both A1 and pim-1 were required to induce interleukin 3-independent cell growth, inhibit activation of caspase 3, and stimulate cell cycle progression. Moreover, simultaneous up-regulation of both A1 and pim-1 was essential for in vitro transformation and in vivo leukemogenesis mediated by BCR/ABL. These data indicate that induction of A1 and pim-1 expression may play a critical role in the BCR/ABL-dependent transformation.