Systemic mastocytosis associated with acute myeloid leukemia: case report and implications for disease pathogenesis

Escribano, Luís; García‐Montero, Andrés C.; Núñez-López, Rosa; López‐Jiménez, Javier; Almeida, Júlia; Prados, Aránzazu; Órfão, Alberto

doi:10.1016/j.jaci.2004.02.042

Cited by 19 publications

(13 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notably, the widely recognised point mutation D816V was not seen in any of the leukemic blasts of patients with MCL or SM with an associated AML whom we studied. The finding is in agreement with the fact that the D816V mutation has been found only sporadically in CBF-AMLs that are frequently accompanied by SM [7,30,50,69]. It is also possible that mutant KIT isoforms 1 and 2 are somehow selectively inhibitory to D816V.…”

Section: Discussionsupporting

confidence: 89%

The identification and characterisation of novelKITtranscripts in aggressive mast cell malignancies and normal CD34+ cells

Ozer

Zhao

Ostler

et al. 2008

Leukemia & Lymphoma

View full text Add to dashboard Cite

KIT mutations have been identified in several malignancies, including acute myeloid leukemia (AML) and systemic mastocytosis (SM). Mast cell leukemia (MCL) is the most aggressive mast cell neoplasm, but has not been well studied due to its rarity. We identified novel KIT transcripts in two patients with MCL and two patients with SM with an associated hematological disorder, but not from two patients with SM. Similar novel KIT transcripts were also observed in normal CD34+ cells from bone marrow and umbilical cord blood, suggesting that altered KIT isoforms may be specific to the blast stage of hematopoietic precursors. The novel KIT proteins lack several domains including the ATP binding site, and one was inactive in a functional test for autophosphorylation. Our discovery of novel KIT transcripts underscores the importance of analysing entire protein encoding regions when studying genes of interest.

show abstract

Section: Discussionsupporting

confidence: 89%

The identification and characterisation of novelKITtranscripts in aggressive mast cell malignancies and normal CD34+ cells

Ozer

Zhao

Ostler

et al. 2008

Leukemia & Lymphoma

View full text Add to dashboard Cite

show abstract

“…Other cytogenetic abnormalities such as translocation t (8; 21) which is usually characteristic of leukemic disease have also been detected in both populations further supporting this hypothesis [5]. Others however have reported different cytogenetic profiles between the two malignant clones, suggesting the presence of a distinct progenitor cell for each [6]. A possible explanation in this case would be that the C-KIT mutation Asp860Val is acquired by a subclone of the leukemic cells that serves as the basis of a mast cell disorder.…”

supporting

confidence: 53%

Mastocytosis causing refractory hypotension after coronary angiography

Manola

Kourelis

Busman

et al. 2012

International Journal of Cardiology

View full text Add to dashboard Cite

“…However, it should be noted that so far, most studies analyzing KIT mutations in SM reported on relatively small series of patients with aggressive forms of the disease 2,3,5,7,9,22,29,30 or single case reports. 6,15,41 Despite this, recent review papers 25,42 estimate that the frequency of the D816V KIT mutation in adult patients with SM could be higher than 80%, while the frequency of KIT mutations in the different forms of SM remains quite variable. 2,3,5,7,9,11,29,30,43 In some studies, such variability could be related to differences in the methods used and/or the type of samples used for the identification of KIT mutations.…”

mentioning

confidence: 99%

KIT mutation in mast cells and other bone marrow hematopoietic cell lineages in systemic mast cell disorders: a prospective study of the Spanish Network on Mastocytosis (REMA) in a series of 113 patients

Garcia-Montero

Jara‐Acevedo

Teodósio

et al. 2006

Blood

447

480

View full text Add to dashboard Cite

Despite the relevance of the c-kit/stem cell factor (SCF) signaling pathway in mast cell (MC) diseases, the exact frequency of KIT mutations in different compartments of bone marrow (BM) hematopoietic cells of individuals with systemic mastocytosis (SM), and its different diagnostic categories, remains unknown. In this study, we prospectively analyzed the presence of KIT mutations in fluorescence-activated cell-sorting (FACS)-purified populations of BM MCs (n ‫؍‬ 113) and other BM cell compartments (n ‫؍‬ 67) from adults with SM. Our results show the presence of D816V KIT mutation in virtually all adults (93%) with indolent and aggressive forms of SM, except welldifferentiated SM (29%), while other KIT mutations were rarely (< 3%) detected. In around one-third of patients with mutated MCs, the KIT mutation was also detected in CD34 ؉ hematopoietic cells and eosinophils, and, to a lesser extent, in monocytic, neutrophil-lineage BM precursor cells and lymphocytes. Most patient with poor-prognosis SM (81%) carried the KIT mutation in 2 or more BM myeloid cell populations, while this was detected in a smaller proportion (27%) of indolent cases. These results would support the notion that KIT mutation is a hallmark of adult SM where it targets a pluripotent hematopoietic stem cell, and may contribute to explaining previously observed discrepancies in the literature. IntroductionMast cell diseases (MCDs) are a heterogeneous group of disorders characterized by an abnormal proliferation and accumulation of mast cells (MCs) in different tissues. In a relatively high proportion of cases, the clonal nature of the disease can be established on the basis of the demonstration of gain-of-function mutations involving the tyrosine kinase domain of c-kit in lesional skin and bone marrow (BM) cells. [1][2][3][4][5][6][7][8][9] Typically, the A71763T substitution is detected, whereby an aspartate is changed for a valine at codon 816 of the c-kit protein sequence. However, other uncommon somatic (V560G, 10 D815K, 11 D816Y, 2,11,12 D816F, 2,11 D816H, 13 and D820G 14 ) and germ-line (F522C, 15 A533D, 16 K509I, 17 and del419 18 ) mutations, which may result in a ligand-independent activation of the stem cell factor receptor, have been reported, most frequently in individual cases. Presence of the KIT mutations in patients with systemic mastocytosis (SM) is not restricted to BM MCs, but it has also been sporadically reported in other non-MC hematopoietic lineages, 7,[19][20][21][22][23][24] suggesting that expansion of clonal MCs may arise from an uncommitted hematopoietic stem cell. However, attempts to demonstrate the presence of KIT mutation in purified CD34 ϩ hematopoietic precursor cells have failed so far. 25 The pathogenetic relevance of the different KIT mutations in MCDs is still not fully understood; however, their identification has become of major prognostic significance 26 due to the availability of protein kinase inhibitors such as imatinib (STI571, Gleevec; Novartis, Basel, Switzerland). These new targeted drugs hav...

show abstract

Systemic mastocytosis associated with acute myeloid leukemia: case report and implications for disease pathogenesis

Cited by 19 publications

References 47 publications

The identification and characterisation of novelKITtranscripts in aggressive mast cell malignancies and normal CD34+ cells

The identification and characterisation of novelKITtranscripts in aggressive mast cell malignancies and normal CD34+ cells

Mastocytosis causing refractory hypotension after coronary angiography

KIT mutation in mast cells and other bone marrow hematopoietic cell lineages in systemic mast cell disorders: a prospective study of the Spanish Network on Mastocytosis (REMA) in a series of 113 patients

Contact Info

Product

Resources

About