CAL2labels the megakaryocytes in myeloproliferative neoplasms (essentialthrombocythaemia (ET) and primary myelofibrosis (PMF)) with CALRmutation and enables to distinguish ET and PMF with CALR mutation frompolycythemia vera (PV), from CALR mutation negative ET and PMF and fromreactive bone marrow.
Why is CAL2 able to detect all known types of CALR mutations?
Alltypes of CALR mutation result in a novel C-terminus. This harbors acommon epitope expressed in all kinds of CALR mutations. The CAL2antibody is directed against this common epitope. Therefore, it can beconcluded that the CAL2 antibody is able to detect all CALR mutations.
CAL2 IHC of four PMF cases:
A and C: Selective staining of mutated CALR protein in megakaryocytes of two PMF cases, respectively in prefibrotic phase and in fibrotic phase, in which Sanger sequencing detected a CALR mutation.
B and D: Absent CAL2 staining in two PMF cases, respectively in prefibrotic and in fibrotic phase, both without molecularly detected mutated CALR. The fibrotic stroma remains unstained (C and D).
A
B
C
D
References
BonifacioM et al. CAL2 Monoclonal Antibody Is a Rapid and Sensitive Assay forthe Detection of Calreticulin Mutations in Essential Thrombocythemia andMay Provide Prognostic Informations. BLOOD 128: 3122, 2016
NomaniL et al. CAL2 Immunohisto-chemical Staining Accurately Identifies CALRMutations in Myeloproliferative Neoplasms. Am J Clin Pathol. 146(4):431-438, 2016.
Andrici J et al. Mutation specificimmuno-histochemistry is highly specific for the presence ofcalreticulin mutations in myeloproliferative neoplasms. Pathology 48(4):319-324, 2016
Stein, H et al. A new monoclonal antibody (CAL2)detects CALRETICULIN mutations in formalin-fixed and paraffin embeddedbone marrow sections. Leukemia 2015, accepted for publication.
NangaliaJ et al. Somatic CALR Mutations in Myeloproliferative Neoplasms withNonmutated JAK2. N Engl J Med 369(25): 2391-2405, 2013.
Klampfl T et al. Somatic Mutations of Calreticulin in Myeloproliferative Neoplasms. N Engl J Med 369(25): 2379-2390, 2013.
Bilder
Selektive IHC-F?rbung von mutiertem CALRETICULIN in Megakaryozyten bei früher prim?rer Myelofibrose (Klon CAL2).Selektive IHC-F?rbung von mutiertem CALRETICULIN in Megakaryozyten bei essentieller Thrombozyth?mie (Klon CAL2).IHC-Nachweis aller Arten von CALRETICULIN Mutationen in MPNs (FFPE Knochenmarkbiopsate) mit dem monklonalen Antikörper CAL2.