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A treatment that alters gene expression overcame chemotherapy resistance and resulted in complete remission in a mouse model of acute myeloid leukemia.

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(University of Texas M. D. Anderson Cancer Center) A combination of the standard-of-care chemotherapy drug known as azacitidine, with nivolumab, an immune checkpoint inhibitor, demonstrated an encouraging response rate and overall survival in patients with relapsed or refractory acute myeloid leukemia (AML) according to findings from a Phase II study at The University of Texas MD Anderson Cancer Center.

Condition:   Acute Myeloid Leukemia Interventions:   Diagnostic Test: Sample Collection Blood;   Diagnostic Test: Stool Sample Sponsor:   Masonic Cancer Center, University of Minnesota Not yet recruiting

Source: ClinicalTrials.govCategory: Research Source Type: clinical trials

Rearrangements of the mixed-lineage-leukemia (MLL) gene at chromosome 11q23 are frequently observed in infantile acute lymphoblastic leukemia (ALL) and therapy-related second leukemia [1,2], and ALL with MLL gene rearrangements (MLL+ALL) is refractory to chemotherapy and its prognosis is still dismal although it has been improved to some extent by performing hematopoietic stem cell transplantation [3,4]. Of interest, MLL+ALL has a unique gene profile clearly distinguishable from other types of ALL and acute myeloid leukemia (AML), and specific genes such as Fms-like tyrosine kinase 3 (FLT3), CD44, LMO2, and HOXA9 are overe…

Source: Leukemia ResearchCategory: Hematology Authors: Tags: Research paper Source Type: research

Acute myeloid leukemia (AML) is one of the most common hematological malignancies [1,2]. Despite the application of new molecular targeted drugs and progress of allogeneic hematopoietic stem cell transplantation, chemoradiotherapy is still the mainstay for the treatment of AML. However, AML cells are demonstrated to unavoidably develop primary or secondary chemo-resistance, thereby resulting in refractory and recurrent disease in patients. So far, most clinical trials of chemotherapy showed very limited benefits for refractory and recurrent AML [3].

Source: Experimental HematologyCategory: Hematology Authors: Source Type: research

Rationale:
The balanced translocation t(8;21;22)(q22;q22;q11.2) is not reported previously, although t(8;21)(q22;q22) is seen in approximately 7% of adults and most frequent abnormality in children with newly diagnosed acute myeloid leukemia (AML). AML-associated hemophagocytic lymphohistiocytosis (HLH) is a rare event, reported only of limited numbers. The present study reports a very rare case of t(8;21;22)(q22;q22;q11.2) with AML, not reported previously, and developed HLH at the same time.
Patient concerns and diagnosis:
A 15-year-old girl presented with a history of bleeding gums and high fever, leukocytosis, ane…

Source: MedicineCategory: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research

We reported here a case of a 46-year-old man who was diagnosed as Ph+ AML. This diagnosis was confirmed by bone marrow pathology and karyotype analysis of 46, XY, t (9; 22). Further examination, molecular genetic analysis showed BCR/ABL1 (p190) without ABL1 kinase domain mutations, and direct evidence demonstrated in AML by flow cytometry.
Diagnosis:
The diagnosis of Ph+ AML was made on May 2016 according to morphology, immunology, cytogenetic, and molecular criteria, and multiple organ failure was also diagnosed.
Interventions:
The patient was treated with dasatinib as the only medication after experiencing multiple…

Source: MedicineCategory: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research

CLEC12A has recently been identified as an antigen, expressed on leukemic stem cells and leukemic blasts. Given the fact that this expression profile seems stable throughout diagnosis, treatment and relapse on leukemic blasts and leukemic stem cells, CLEC12A can be considered a highly potent and reliable marker for the detection of measurable residual disease and therefore applicable for risk stratification and prognostication in AML. Low CLEC12A expression on leukemic blasts seems to be independently associated with lower likelihood of achieving complete remission after 1  cycle of induction chemotherapy, shorter event …

Source: Blood ReviewsCategory: Hematology Authors: Tags: Review Source Type: research

Older adults with acute myeloid leukemia treated with intensive chemotherapy: “old” prognostic algorithms may not apply.
Haematologica. 2018 Nov;103(11):1758-1759
Authors: Stone RM, Lindsley C
PMID: 30381416 [PubMed – in process]

Source: HaematologicaCategory: Hematology Authors: Tags: Haematologica Source Type: research

Abstract
Clonal hematopoiesis (CH), in which stem cell clones dominate blood production, becomes increasingly common with age and can presage malignancy development. The conditions that promote ascendancy of particular clones are unclear. We found that mutations in PPM1D (protein phosphatase Mn2+/Mg2+-dependent 1D), a DNA damage response regulator that is frequently mutated in CH, were present in one-fifth of patients with therapy-related acute myeloid leukemia or myelodysplastic syndrome and strongly correlated with cisplatin exposure. Cell lines with hyperactive PPM1D mutations expand to outcompete normal cells …

Source: Cell Stem CellCategory: Stem Cells Authors: Tags: Cell Stem Cell Source Type: research

ConclusionsThis analysis suggests that midostaurin is a cost-effective treatment for adult patients with newly diagnosedFLT3-mutated AML, from a US third-party payer perspective.

Source: PharmacoEconomicsCategory: Health Management Source Type: research

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