Pernio as the presenting sign of blast crisis in acute lymphoblastic leukemia

2017 ◽  
Vol 35 (1) ◽  
pp. e74-e75 ◽  
Author(s):  
Kelly K. Park ◽  
Bailey Tayebi ◽  
Lily Uihlein ◽  
Jodi Speiser ◽  
Adnan Mir ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Blast Crisis

Meningeal Leukemia following Lymphoid Blast Crisis in Chronic Myeloid Leukemia: Therapeutic Implications

1982 ◽  
Vol 68 (3) ◽  
pp. 257-263 ◽  
Author(s):  
Mario Cazzola ◽  
Giulio Nalli ◽  
Ercole Brusamolino ◽  
Maurizio Daccò ◽  
Angela Ghizzi ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Chronic Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Blast Crisis ◽  
Early Prevention ◽  
Therapeutic Implications ◽  
Therapeutic Protocol ◽  
Meningeal Leukemia

Five of 40 patients with chronic myeloid leukemia (CML) had lymphoid blast crisis and 4 of them achieved complete remission of metamorphosis with vincristine and prednisone. While in hematologic remission, two of these subjects developed meningeal leukemia. Clinical and biologic data indicated that the course of the disease after lymphoid blast crisis was very similar to that of acute lymphoblastic leukemia (ALL). It is suggested that patients with CML who develop lymphoid blast crisis should be treated with an intensive therapeutic protocol including early prevention of meningeal leukemia.

scholarly journals The receptor tyrosine kinase p185HER2 is expressed on a subset of B- lymphoid blasts from patients with acute lymphoblastic leukemia and chronic myelogenous leukemia

Blood ◽  
1995 ◽  
Vol 86 (5) ◽  
pp. 1916-1923 ◽  
Author(s):  
HJ Buhring ◽  
I Sures ◽  
B Jallal ◽  
FU Weiss ◽  
FW Busch ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Tyrosine Kinase ◽  
Cell Lines ◽  
Receptor Tyrosine Kinase ◽  
Lymphoblastic Leukemia ◽  
Blast Crisis ◽  
Hematopoietic Cell ◽  
Myelogenous Leukemia ◽  
Leukemic Cells ◽  
B Lymphoid

The class I receptor tyrosine kinase (RTK) HER2 is an oncoprotein that is frequently involved in the pathogenesis of tumors of epithelial origin. Here we report mRNA expression in peripheral blood and bone marrow cells from healthy donors in hematopoietic cell lines and leukemic blasts from patients with acute lymphoblastic leukemia (ALL), acute myeloblastic leukemia (AML), chronic lymphoblastic leukemia (CLL), and chronic myeloid leukemia (CML). However, cell surface expression of HER2 protein (p185HER2) was found exclusively on a subset of leukemic cells of the B-lymphoblastic lineage. p185HER2 expression was found on blasts in 2 of 15 samples from infants, 9 of 19 samples from adult patients with C-ALL (CD19+CD10+), and 1 of 2 samples from patients with pro-B ALL (CD19+CD10-), whereas none of the leukemic cells from patients with AML (0/30), T-ALL (0/7), CLL (0/5) (CD19+CD5+), or CML in chronic and accelerated phase (0/5) or in blast crisis with myeloid differentiation (0/14) were positive for p185HER2. However, cells from 3 of 4 patients with CML in B-lymphoid blast crisis (CD19+CD10+) expressed high levels of p185HER2, which was also found on the surface of the CML-derived B-cell lines BV-173 and Nalm-1. Our study shows p185HER2 expression on malignant cells of hematopoietic origin for the first time. Aberrant expression of this oncogenic receptor tyrosine kinase in hematopoietic cell types may be an oncogenic event contributing to the development of a subset of B- lymphoblastic leukemias.

Potential Targeting Ph+ Acute Lymphoblastic Leukemia Stem and Progenitor Cells By Modulating the CIP2A-SET-SETBP1 -Mediated Suppression of PP2A Activity

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2909-2909
Author(s):  
Justine Yu ◽  
Giovannino Silvestri ◽  
Lorenzo Stramucci ◽  
Masashi Sanada ◽  
Tomoyuki Yamaguchi ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Kinase Inhibitors ◽  
Lymphoblastic Leukemia ◽  
Blast Crisis ◽  
Philadelphia Chromosome ◽  
Aberrant Expression ◽  
Self Renewal ◽  
Interacting Protein ◽  
Pp2a Activity ◽  
Almost All

Abstract Tyrosine kinase inhibitors (TKIs) combined with chemotherapy significantly improved outcomes in adult Philadelphia-chromosome-positive (Ph+) B-cell Acute Lymphoblastic Leukemia (B-ALL). However, high relapse rates due to development of TKI resistance or chemotherapy-induced adverse effects remain the major therapeutic challenges. Furthermore, all TKIs are not effective against Ph+leukemia-initiating cells (LICs). The tumor suppressor protein phosphatase 2A (PP2A) is inactive in almost all solid and hematopoietic tumors. Suppression of PP2A activity correlates with poor outcome and disease progression, and largely relies on the aberrant expression of CIP2A, SET and/or SETBP1. SETBP1 was discovered as a SET-interacting protein, and recently described as mutated or overexpressed in several myeloid malignancies where it acts as an independent negative prognostic factor and as an inhibitor of PP2A, however its role in lymphoid malignancies is still unknown. Thus, we postulated that SETBP1 regulates survival and self-renewal of Ph+B-ALL LICs and progenitors through inhibition of PP2A. We reported that BCR-ABL1 kinase-dependent and -independent mechanisms induce SET-dependent PP2A inhibition in Ph+ (CMLand B-ALL) progenitors and quiescent TKI-resistant CML LICs, respectively, and that SET downregulation or pharmacologic (i.e. SET-interacting PP2A-activating drugs; PADs) restoration of PP2A activity strongly impaired malignant but not normal hematopoiesis by selectively killing Ph+progenitors (CML and ALL) and TKI-resistant quiescent stem (CML) cells. Here, we show that wild type SETBP1 is markedly induced in an imatinib (IM)-insensitive manner in primary CD34+CD19+ Ph+ B-ALL progenitors and Ph+ B-ALL cell lines (BV173 and SUP-B15) and barely detectable in CD34+ cells from CML patients in chronic and blastic phase. Overexpression of SETBP1 was found essential for PP2A inhibition in Ph+ B-ALL blasts. Accordingly, shRNA-dependent SETBP1 downregulation impaired clonogenic potential and self-renewal of CD34+CD19+ Ph+ B-ALL cells in CFC and serial replating assays. Furthermore, we have evidence that a SETBP1-SET/CIP2A inhibitory complex may exist in Ph+ cells, suggesting that SETBP1 might serve to recruit SET and CIP2A to suppress PP2A activity. Indeed, we found that CIP2A, like SET and SETBP1, is also overexpressed in CD34+CD19+ Ph+ B-ALL compared to CD34+CD19+cell from BM of healthy donors. Because, SETBP1 stabilizes SET and augments PP2A inhibition, and ectopic SETBP1 expression confers self-renewal to mouse myeloid progenitors and cooperates with BCR-ABL1 to induce a CML blast crisis-like disease in mice, our data suggest that aberrant SETBP1 expression might significantly contributes to the development of Ph+ B-ALL and persistence of TKI-resistant Ph+ B-ALL LICs. Disclosures Milojkovic: Ariad: Honoraria; BMS: Honoraria; Pfizer: Honoraria; Novartis: Honoraria. Roy:Paladin: Consultancy; Fate Therapeutics: Consultancy; Novartis: Consultancy; Kiadis Pharma: Research Funding.

scholarly journals Clinical Implication of BCR/ABL Fusion Transcript Monitoring in Addition to Ig/TCR Gene Rearrangement-Based Minimal Residual Disease in Philadelphia Chromosome-Positive Childhood Acute Lymphoblastic Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2258-2258
Author(s):  
Kirsten Bleckmann ◽  
Julia Alten ◽  
Anja Moericke ◽  
Andishe Attarbashi ◽  
Andrea Teigler-Schlegel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Blast Crisis ◽  
Philadelphia Chromosome ◽  
Fusion Transcript ◽  
Minimal Residual

Abstract Background: Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) accounts for about 3% of pediatric ALL and has a poor prognosis. Advances of treatment due to the tyrosine kinase inhibitor imatinib have improved the cure rates. According to recent guidelines in the amended European intergroup trial on Ph+ ALL (EsPhALL), patients with rapid minimal residual disease (MRD) response and negativity during further treatment are no longer eligible for allogeneic stem cell transplantation (alloSCT). This down-grading of therapy in a circumscribed patient cohort with favorable prognosis is a desirable development as stem cell transplantation still implies a considerable risk of toxicity. These guidelines refer to MRD by immunoglobulin/T-cell receptor (Ig/TCR) gene rearrangements and do not consider monitoring of the BCR/ABL fusion transcript as long as informative results for Ig/TCR MRD are available. However, discrepancies between the results of the two methods occur. This complicates the decision on alloSCT indication if Ig/TCR MRD becomes negative while the BCR/ABL fusion transcript remains detectable. Objectives/Methods: We therefore evaluated the prognostic relevance of this specific combination of findings, i.e. the continuous negativity for Ig/TCR MRD and persistently positive results for BCR/ABL after the second intensive consolidation block or later, in 16 pediatric patients with Ph+ ALL. They were identified among 139 German and Austrian Ph+ patients treated in the ALL-BFM 2000 or EsPhALL trial from August 1, 1999 to July 31, 2013. Twelve out of the 16 patients received imatinib in first-line treatment intermittently as previously described in the EsPhALL protocol (Biondi A et al Lancet Oncol. 2012) or continuously as recommended by the amended EsPhALL protocol. Results: Eight of the 16 identified patients received an alloSCT in first complete remission (1st CR), whereas the remaining eight patients were treated with chemotherapy only. Of the eight patients with alloSCT, seven are in first continuous complete remission (1st CCR) with median EFS of 7.6 years, one patient died after second relapse. In the group of eight patients without alloSCT three are in 1st CCR with a median EFS of 2.6 years, four patients are in 2nd CR after relapse (3/4 had alloSCT in 2nd CR, median EFS 4.7 years), and one patient with Down syndrome died of an infectious complication. Remarkably, two patients of the latter group (both with M-BCR) showed a protracted increase of BCR/ABL copy numbers over several years with neither morphological signs of relapse nor Ig/TCR MRD based reappearance. One of them eventually suffered a relapse 5 years after diagnosis, one is still in 1st CCR with EFS of 5.2 years. Conclusion: The data suggest that patients with Ig/TCR MRD negativity and persistently detectable BCR/ABL fusion transcript have a high risk of relapse when treated with chemotherapy only and may benefit from alloSCT. However, patient numbers are currently too small to deduce recommendations from this observation. Further investigation of a larger cohort with longer follow-up is needed to confirm the prognostic importance of BCR/ABL fusion transcript monitoring in addition to Ig/TCR MRD, especially considering a potential additional impact of the recently implemented continuous imatinib treatment. One additional patient would have met the diagnostic inclusion criteria of this analysis. He had an extensive increase of BCR/ABL fusion transcript at the end of maintenance treatment while being in morphological remission and negative for Ig/TCR MRD. This patient proved to be BCR/ABL positive in granulocytes revealing a chronic myeloid leukemia (CML) misdiagnosed as ALL during initial blast crisis. This indicates that an underlying CML might be taken into consideration also in other patients of the analyzed cohort. In consequence, BCR/ABL in granulocytes is now tested in all newly diagnosed Ph+ ALL patients in Germany to ensure the differentiation of BCR/ABL positive ALL vs. CML in blast crisis. Disclosures No relevant conflicts of interest to declare.

Diagnosis of acute lymphoblastic leukemia from intracerebral hemorrhage and blast crisis. A case report and review of the literature

2010 ◽  
Vol 112 (7) ◽  
pp. 575-577 ◽  
Author(s):  
Matthew R. Naunheim ◽  
Brian V. Nahed ◽  
Brian P. Walcott ◽  
Kristopher T. Kahle ◽  
Chad P. Soupir ◽  
...  
Keyword(s):  
Case Report ◽  
Acute Lymphoblastic Leukemia ◽  
Intracerebral Hemorrhage ◽  
Lymphoblastic Leukemia ◽  
Blast Crisis ◽  
Review Of The Literature
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