Imatinib improves but may not fully reverse the poor prognosis of patients with CML with derivative chromosome 9 deletions

Deletions of the derivative chromosome 9 have recently been reported in chronic myeloid leukemia. These deletions are large, occur at the time of the Philadelphia (Ph) translocation, span the translocation breakpoint, and represent a powerful prognostic indicator. However, the molecular mechanisms responsible for the poor prognosis associated with deletions are obscure, and several possible models are investigated here. First, we demonstrate that all derivative chromosome 9 deletions detected by fluorescence in situ hybridization were associated with an absence ofABL-BCR expression. However, loss ofABL-BCR expression also occurred without an overt deletion, suggesting the existence of other mechanisms by whichABL-BCR transcription can be abolished. Furthermore, analysis of survival in 160 patients demonstrated that loss ofABL-BCR expression, in contrast to deletion status, was not an indicator of poor prognosis. Second, we addressed the possibility that concomitant small deletions of the Ph chromosome modulateBCR-ABL transcription. Real-time reverse-transcription polymerase chain reaction was used to demonstrate that derivative chromosome 9 deletions were not accompanied by altered levels of BCR-ABL transcripts. Third, deletions may represent a consequence of genetic instability within the target cell at the time of the Ph translocation, with the poor prognosis reflecting a predisposition to subsequent additional genetic alterations. However, patients with deletions do not exhibit an increased frequency of secondary cytogenetic changes following disease progression. Taken together, these data support a model in which deletions of the derivative chromosome 9 result in rapid disease progression as a result of the loss of one or more genes within the deleted region.

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Deletions of the derivative chromosome 9 do not account for the poor prognosis associated with Philadelphia-positive acute lymphoblastic leukemia

Blood ◽

10.1182/blood.v99.6.2274 ◽

2002 ◽

Vol 99 (6) ◽

pp. 2274-2275 ◽

Cited By ~ 8

Author(s):

Alistair G. Reid ◽

Brian J. P. Huntly ◽

Eveline Hennig ◽

Dietger Niederwieser ◽

Lynda J. Campbell ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Poor Prognosis ◽

Lymphoblastic Leukemia ◽

Chromosome 9 ◽

Derivative Chromosome ◽

The Poor

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The Effect of Heterogenous Subregions in Glioblastomas on Survival Stratification: A Radiomics Analysis Using the Multimodality MRI

Technology in Cancer Research & Treatment ◽

10.1177/15330338211033059 ◽

2021 ◽

Vol 20 ◽

pp. 153303382110330

Author(s):

Lulu Yin ◽

Yan Liu ◽

Xi Zhang ◽

Hongbing Lu ◽

Yang Liu

Keyword(s):

Poor Prognosis ◽

Intratumor Heterogeneity ◽

Short Term ◽

Prognostic Information ◽

Manual Delineation ◽

Flair Sequence ◽

The Poor ◽

Contrast Enhanced ◽

Mri Sequences

Intratumor heterogeneity is partly responsible for the poor prognosis of glioblastoma (GBM) patients. In this study, we aimed to assess the effect of different heterogeneous subregions of GBM on overall survival (OS) stratification. A total of 105 GBM patients were retrospectively enrolled and divided into long-term and short-term OS groups. Four MRI sequences, including contrast-enhanced T1-weighted imaging (T1C), T1, T2, and FLAIR, were collected for each patient. Then, 4 heterogeneous subregions, i.e. the region of entire abnormality (rEA), the regions of contrast-enhanced tumor (rCET), necrosis (rNec) and edema/non-contrast-enhanced tumor (rE/nCET), were manually drawn from the 4 MRI sequences. For each subregion, 50 radiomics features were extracted. The stratification performance of 4 heterogeneous subregions, as well as the performances of 4 MRI sequences, was evaluated both alone and in combination. Our results showed that rEA was superior in stratifying long-and short-term OS. For the 4 MRI sequences used in this study, the FLAIR sequence demonstrated the best performance of survival stratification based on the manual delineation of heterogeneous subregions. Our results suggest that heterogeneous subregions of GBMs contain different prognostic information, which should be considered when investigating survival stratification in patients with GBM.

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Umbilical cord blood transplantation can overcome the poor prognosis of KMT2A-MLLT3 acute myeloid leukemia and can lead to good GVHD-free/relapse-free survival

Annals of Hematology ◽

10.1007/s00277-021-04413-2 ◽

2021 ◽

Author(s):

Juan Tong ◽

Lei Zhang ◽

Huilan Liu ◽

Xiucai Xu ◽

Changcheng Zheng ◽

...

Keyword(s):

Myeloid Leukemia ◽

Poor Prognosis ◽

Cord Blood Transplantation ◽

Chronic Gvhd ◽

Relapse Free Survival ◽

Free Survival ◽

Chemotherapy Group ◽

Blood Transplantation ◽

The Poor ◽

First Complete Remission

AbstractThis is a retrospective study comparing the effectiveness of umbilical cord blood transplantation (UCBT) and chemotherapy for patients in the first complete remission period for acute myeloid leukemia with KMT2A-MLLT3 rearrangements. A total of 22 patients were included, all of whom achieved first complete remission (CR1) through 1–2 rounds of induction chemotherapy, excluding patients with an early relapse. Twelve patients were treated with UCBT, and 10 patients were treated with chemotherapy after 2 to 4 courses of consolidation therapy. The 3-year overall survival (OS) of the UCBT group was 71.3% (95% CI, 34.4–89.8%), and that of the chemotherapy group was 10% (95% CI, 5.89–37.3%). The OS of the UCBT group was significantly higher than that of the chemotherapy group (P = 0.003). The disease-free survival (DFS) of the UCBT group was 60.8% (95% CI, 25.0–83.6%), which was significantly higher than the 10% (95% CI, 5.72–35.8%) of the chemotherapy group (P = 0.003). The relapse rate of the UCBT group was 23.6% (95% CI, 0–46.8%), and that of the chemotherapy group was 85.4% (95% CI, 35.8–98.4%), which was significantly higher than that of the UCBT group (P < 0.001). The non-relapse mortality (NRM) rate in the UCBT group was 19.8% (95% CI, 0–41.3%), and that in the chemotherapy group was 0.0%. The NRM rate in the UCBT group was higher than that in the chemotherapy group, but there was no significant difference between the two groups (P = 0.272). Two patients in the UCBT group relapsed, two died of acute and chronic GVHD, and one patient developed chronic GVHD 140 days after UCBT and is still alive, so the GVHD-free/relapse-free survival (GRFS) was 50% (95% CI, 17.2–76.1%). AML patients with KMT2A-MLLT3 rearrangements who receive chemotherapy as their consolidation therapy after CR1 have a very poor prognosis. UCBT can overcome the poor prognosis and significantly improve survival, and the GRFS for these patients is very good. We suggest that UCBT is a better choice than chemotherapy for KMT2A-MLLT3 patients.

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Socioeconomic factors may contribute to the poor prognosis observed among women with advanced ovarian carcinoma treated with neoadjuvant chemotherapy

Gynecologic Oncology ◽

10.1016/j.ygyno.2008.07.079 ◽

2008 ◽

Vol 111 (2) ◽

pp. 380-381

Author(s):

D.M. Chase ◽

A. Rincon ◽

M. Deane ◽

K.S. Tewari ◽

W.R. Brewster

Keyword(s):

Neoadjuvant Chemotherapy ◽

Ovarian Carcinoma ◽

Socioeconomic Factors ◽

Poor Prognosis ◽

Advanced Ovarian Carcinoma ◽

The Poor

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Elevated antigen-specific Th2 type response is associated with the poor prognosis of hand, foot and mouth disease

Virus Research ◽

10.1016/j.virusres.2013.07.009 ◽

2013 ◽

Vol 177 (1) ◽

pp. 62-65 ◽

Cited By ~ 13

Author(s):

Ruicheng Wei ◽

Lijuan Xu ◽

Na Zhang ◽

Kai Zhu ◽

Juhao Yang ◽

...

Keyword(s):

Poor Prognosis ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

The Poor ◽

Foot And Mouth ◽

Type Response

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Evaluation of serum ATX and LPA as potential diagnostic biomarkers in patients with pancreatic cancer

BMC Gastroenterology ◽

10.1186/s12876-021-01635-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Jiang Chen ◽

Hongyu Li ◽

Wenda Xu ◽

Xiaozhong Guo

Keyword(s):

Pancreatic Cancer ◽

Poor Prognosis ◽

Prognostic Value ◽

Potential Role ◽

Early Stage ◽

Serum Levels ◽

Diagnostic Efficacy ◽

Diagnostic Biomarkers ◽

The Poor

Abstract Background Pancreatic cancer (PC) is a devastating disease that has a poor prognosis and a total 5-year survival rate of around 5%. The poor prognosis of PC is due in part to a lack of suitable biomarkers that can allow early diagnosis. The lysophospholipase autotaxin (ATX) and its product lysophosphatidic acid (LPA) play an essential role in disease progression in PC patients and are associated with increased morbidity in several types of cancer. In this study, we evaluated both the potential role of serum LPA and ATX as diagnostic markers in PC and their prognostic value for PC either alone or in combination with CA19-9. Methods ATX, LPA and CA19-9 levels were evaluated using ELISA of serum obtained from PC patients (n = 114) healthy volunteers (HVs: n = 120) and patients with benign pancreatic diseases (BPDs: n = 94). Results Serum levels of ATX, LPA and CA19-9 in PC patients were substantially higher than that for BPD patients or HVs (p < 0.001). The sensitivity of LPA in early phase PC was 91.74% and the specificity of ATX was 80%. The levels of ATX, LPA and CA19-9 were all substantially higher for early stage PC patients compared to levels in serum from BPD patients and HVs. The diagnostic efficacy of CA19-9 for PC was significantly enhanced by the addition of ATX and LPA (p = 0.0012). Conclusion Measurement of LPA and ATX levels together with CA19-9 levels can be used for early detection of PC and diagnosis of PC in general.

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Dedifferentiated chondrosarcoma: A report of the clinicopathologic features and outcomes of 16 cases treated at a single institution.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e23500 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e23500-e23500

Author(s):

Charles Gusho ◽

Steven Gitelis ◽

Alan T. Blank

Keyword(s):

Poor Prognosis ◽

Nonoperative Management ◽

Clinicopathological Features ◽

Clinicopathologic Features ◽

Single Institution ◽

Dedifferentiated Chondrosarcoma ◽

Wide Margin ◽

The Poor ◽

Kaplan Meier ◽

Period Data

e23500 Background: Dedifferentiated chondrosarcoma (DCS) is a rare and aggressive malignancy with a poor prognosis. The purpose of this investigation was to assess the clinicopathological features and outcomes of DCS patients treated at a single institution. Methods: This study was a retrospective review over a consecutive twenty-year period. Data including treatment details and outcomes were recorded. Results: A total of 16 cases from 2000 to 2018 were reviewed. The median age was 62 years (IQR, 52-69 years) and the majority of DCS arose in the femur (50%, n = 8) and pelvis (25%, n = 4). Fourteen (88%) cases received limb salvage/wide margin resection (n = 13) or intralesional surgery (n = 1). For all DCS, the median estimated overall survival (OS) was 46 months (95% CI, 1-90 months) with both a five and ten-year survival probability of 32%. On Kaplan-Meier analysis there was no difference between operative versus nonoperative management (p = 0.747), surgery alone versus surgery/chemotherapy (p = 0.265), nor surgery alone versus surgery/chemotherapy/radiation (p = 0.698). Conclusions: Our findings confirm the poor prognosis of DCS patients, though with a five-year estimate of 32%, higher than previous literature. Together with existing literature, our data may enable future strategic recommendation of DCS patients.

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