Project description:•The case demonstrated a rare event of clonal heterogeneity by IKZF1 gene status in BCRABL1- ALL.•IKZF1 deletions are secondary events in ALL caused by clonal evolution during the treatment.•It's prognostic significance could be more crucial in BCR-ABL- rather than in BCR-ABL + ALL.•IKZF1 gene alterations may be determined and proved at the genome, expression and protein level.•IKZF1 deletions are suitable for MRD detection but not stable compared to Ig/TCR rearrangement.

| S-EPMC4962816 | biostudies-literature

Negative Impact of Gemtuzumab Ozogamicin on CD33-Positive Early T-Cell Precursor Acute Lymphoblastic Leukemia: A Case Report.

Project description:IntroductionEarly T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a rare subtype of T-cell leukemia that phenotypically expresses mature T-cell markers and immature myeloid markers such as CD33. Gemtuzumab ozogamicin (GO) is a novel agent for the CD33 molecular targeting antibody conjugated to the cytotoxic agent calicheamicin. GO is anticipated to be effective against ETP-ALL. In vivo studies promise antileukemic effects in cell lines; however, clinical reports to support this research are lacking. We treated a patient who suffered from CD33-positive ETP-ALL using GO.Case presentationWe treated an 81-year-old man who suffered from ETP-ALL. The patient's leukemia expressed T cell and myeloid markers including cyCD3, CD5, CD7, CD33, and HLA-DR. Initially, the patient was treated using a standard chemotherapy regimen for acute lymphoblastic leukemia comprising cyclophosphamide, daunorubicin, vincristine, l-asparaginase, and prednisolone. The induction chemotherapy produced the expected complete hematological response; however, bone marrow blasts remained. Following consolidation chemotherapy, the patient maintained a full hematological response. Thereafter, we changed the consolidation regimen to nelarabine, which did not reduce bone marrow blasts effectively. After two courses of nelarabine therapy, we finally used GO at an 8 mg/m2 weekly dose after confirming that CD33 expression was still positive in the patient's residual leukemic cells. GO was ineffective in treating the patient's leukemia, and peripheral blasts increased 30 days following treatment. The patient died 81 days after initiating GO therapy.ConclusionThis is the first clinical case of GO having a negative impact on ETP-ALL. Because the GO resistance mechanism for ETP-ALL has not been fully elucidated, treatment modification should be considered to achieve optimal clinical efficacy.

| S-EPMC10869147 | biostudies-literature

Early precursor T-cell acute lymphoblastic leukemia: current paradigms and evolving concepts.

Project description:Early precursor T cell-acute lymphoblastic leukemia (ETP-ALL) is a rare entity characterized by chemo-resistance and a paucity of data regarding optimal management. We review here the literature regarding the management of ETP-ALL and focus on the recent, emerging data, regarding the potential role of molecularly targeted approaches with a focus on venetoclax.

| S-EPMC7370557 | biostudies-literature

Venetoclax-ponatinib for T315I/compound-mutated Ph+ acute lymphoblastic leukemia.

Project description: Not available

| S-EPMC8799711 | biostudies-literature

Molecular response with blinatumomab in relapsed/refractory B-cell precursor acute lymphoblastic leukemia.

Project description:Minimal residual disease (MRD), where leukemic cell levels are lower than the morphologic detection threshold, is the most important prognostic factor for acute lymphoblastic leukemia (ALL) relapse during first-line chemotherapy treatment and is standard of care in treatment monitoring and decision making. Limited data are available on the prognostic value of MRD response after relapse. We evaluated the relationship between MRD response and outcomes in blinatumomab-treated adults with relapsed/refractory (R/R) B-cell precursor ALL. Of 90 patients with complete remission (CR) or CR with partial hematologic recovery (CRh), 64 (71.1%) achieved a complete MRD response (no detectable individual rearrangements of immunoglobulin/T-cell receptor genes by polymerase chain reaction [PCR] at a minimum sensitivity level of 10-4). Eleven patients had MRD <10-4. Therefore, overall, 75 (83.3%) experienced an MRD response (no detectable MRD or detectable MRD) measured by PCR within the first 2 treatment cycles. Overall survival (OS) and relapse-free survival (RFS) were significantly longer in patients who achieved CR/CRh and MRD response (median, 20.6 and 9.0 months, respectively) compared with CR/CRh patients without MRD response (median, 12.5 and 2.3 months, respectively). In conclusion, longer durations of OS and RFS associated with MRD response support the value of achieving MRD response and its use as a prognostic factor for blinatumomab treatment in R/R ALL. This trial was registered at www.clinicaltrials.gov as #NCT01466179.

| S-EPMC6849936 | biostudies-literature

Combined Application of Pan-AKT Inhibitor MK-2206 and BCL-2 Antagonist Venetoclax in B-Cell Precursor Acute Lymphoblastic Leukemia.

Project description:Aberrant PI3K/AKT signaling is a hallmark of acute B-lymphoblastic leukemia (B-ALL) resulting in increased tumor cell proliferation and apoptosis deficiency. While previous AKT inhibitors struggled with selectivity, MK-2206 promises meticulous pan-AKT targeting with proven anti-tumor activity. We herein, characterize the effect of MK-2206 on B-ALL cell lines and primary samples and investigate potential synergistic effects with BCL-2 inhibitor venetoclax to overcome limitations in apoptosis induction. MK-2206 incubation reduced AKT phosphorylation and influenced downstream signaling activity. Interestingly, after MK-2206 mono application tumor cell proliferation and metabolic activity were diminished significantly independently of basal AKT phosphorylation. Morphological changes but no induction of apoptosis was detected in the observed cell lines. In contrast, primary samples cultivated in a protective microenvironment showed a decrease in vital cells. Combined MK-2206 and venetoclax incubation resulted in partially synergistic anti-proliferative effects independently of application sequence in SEM and RS4;11 cell lines. Venetoclax-mediated apoptosis was not intensified by addition of MK-2206. Functional assessment of BCL-2 inhibition via Bax translocation assay revealed slightly increased pro-apoptotic signaling after combined MK-2206 and venetoclax incubation. In summary, we demonstrate that the pan-AKT inhibitor MK-2206 potently blocks B-ALL cell proliferation and for the first time characterize the synergistic effect of combined MK-2206 and venetoclax treatment in B-ALL.

| S-EPMC7967241 | biostudies-literature

Venetoclax plus low-intensity chemotherapy for adults with acute lymphoblastic leukemia∗

Project description: Not available

| S-EPMC11847096 | biostudies-literature

The Emerging Role of Venetoclax-Based Treatments in Acute Lymphoblastic Leukemia.

Project description:Venetoclax, a B-cell lymphoma (BCL-2) inhibitor, in combination with hypomethylating agents has become the new standard of care in elderly and unfit patients with acute myeloid leukemia, with significantly improved overall survival and quality of life. Studies of venetoclax combined with high-dose chemotherapy are emerging with evidence of higher rates of molecular remission. Recently, a growing number of publications bring forth the use of venetoclax in patients with acute lymphoblastic leukemia (ALL). In the current review, we present the biological rationale of BCL-2 inhibition in ALL, how the interplay of BH3 proteins modulate the response and the current clinical experience with various combinations.

| S-EPMC9504828 | biostudies-literature

Pharmacogenetics of minimal residual disease response in children with B-precursor acute lymphoblastic leukemia: a report from the Children's Oncology Group.

Project description:Minimal residual disease (MRD) as a marker of antileukemic drug efficacy is being used to assess risk status and, in some cases, to adjust the intensity of therapy. Within known prognostic categories, the determinants of MRD are not known. We measured MRD by flow cytometry at day 8 (in blood) and at day 28 (in bone marrow) of induction therapy in more than 1000 children enrolled in Pediatric Oncology Group therapy protocols 9904, 9905, and 9906. We classified patients as "best risk" if they had cleared MRD by day 8 of therapy and as "worst risk" if they had MRD remaining in bone marrow at day 28, and tested whether MRD was related to polymorphisms in 16 loci in genes hypothesized to influence response to therapy in acute lymphoblastic leukemia (ALL). After adjusting for known prognostic features such as presence of the TEL-AML1 rearrangement, National Cancer Institute (NCI) risk status, ploidy, and race, the G allele of a common polymorphism in chemokine receptor 5 (CCR5) was associated with more favorable MRD status than the A allele (P = .009, logistic regression), when comparing "best" and "worst" risk groups. These data are consistent with growing evidence that both acquired and host genetics influence response to cancer therapy.

| S-EPMC2265447 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data