• 2018-07
  • 2019-04
  • Although the NCCN IPI is a promising simple


    Although the NCCN-IPI is a promising simple scale based on conventional clinical factors, its usefulness remains controversial [6,7]. It should be evaluated in populations of different regions and ethnicities before adopting it for routine clinical use.
    Conflict of interest
    Report At presentation, her complete blood count was as follows: hemoglobin 16.8g/dL, hematocrit 49.8%, MCV 107.9fL, MCH 36.4pg, RDW 13%, leukocytes 7.6×109/L, platelets 171×109/L; with a differential showing granulocytes 72%, lymphocytes 17%, monocytes 9%, eosinophils 1%, basophils 1%. Other laboratory values were as follows: TSH 0.34μIU/mL, fT4 1.9ng/dL, vitamin B12 294pg/mL, folate 7.8ng/mL, and erythropoietin 15.6mIU/mL. The patient’s erythrocytosis has persisted for three years since the initial encounter, and has been treated with phlebotomy alone. Initially the patient received weekly phlebotomies. Currently, the patient receives phlebotomies as needed, with a target hematocrit of less than 45% [1].
    Discussion The aa-dutp 14 JAK2 V617F mutation is seen in 95% of all PV patients, and approximately 50% of patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF) [2]. About 3% of the patients have JAK2 exon 12 mutations. Patients with exon 12 mutations often present with isolated erythrocytosis and may not meet the diagnostic criteria for polycythemia vera [3–5]. In addition to these mutations, Ma et al. discovered several mutations in the pseudokinase domain coding region of JAK2 including the G571S mutation in exon 13 [6]. The JAK2 G571S mutation is next to a tyrosine residue at position 570 (Y570). Y570 lies within the JH2 inhibitory domain and is thought to be the most important phosphorylation site for downregulation of JAK2 activity [7,8]. Biochemical studies show that autophosphorylation of Y570 rapidly downregulates kinase activity. The adjacent G571S mutation may cause a confirmation change preventing Y570 phosphorylation, leading to constitutive JAK2 signaling. However, classical in vitro studies do not show activation of STAT5 [9] suggesting that the activating effect of the G571S mutation would be weak. The G571S mutation is extremely rare. In the study by Ma et al. [6] approximately 20,000 blood samples from patients with suspected myeloproliferative neoplasms were analyzed for JAK2 mutations. The G571S mutation was found in only 3 samples, compared to the V617F mutation which was positive in 4280 samples. A recent report describes a family with germline G571S mutations [10], none of whom showed erythrocytosis. The G571S mutation was also found in two patients with “triple-negative” ET and PMF [9]. To our knowledge this is the first case description of a patient with erythrocytosis and a G571S JAK2 mutation. Based on the limited penetrance [10] and in vitro studies [9], it is unlikely that the G571S mutation is the sole driver of erythropoiesis. We hope that this report will facilitate additional studies of patients with the G571S and related exon 13 JAK2 mutations, so as to ascertain their role in the pathogenesis of myeloproliferative disorders.
    Introduction Leukemia which occurs in the first month of life (congenital leukemia) is a rare event, with an estimated incidence of 1 in 5 million births [1]. Congenital leukemias constitute a subset of infant leukemia where a significant percentage of cases show rearrangements involving the MLL (KMT2A) oncogene [2]. These rearrangements presumably arise in utero, and this leukemia subtype is notable for having the lowest somatic mutation burden of any human malignancy measured thus far [3]. Despite this, outcomes remain poor, and novel approaches to the treatment of this leukemia are needed. We describe an unusual case of congenital leukemia with lineage switch following treatment, CNS involvement, and a cryptic MLL rearrangement detectable only by RT-PCR.
    Case study A full term male was born to a 29-year-old G2P2 mother with an unremarkable prenatal course. He was 7 pounds 14 ounces at birth with normal APGAR scores at 1 and 5min. On physical exam, he was noted to have nodular purpuric lesions on his trunk and face, despite a non-traumatic delivery, and marked hepatosplenomegaly. A complete blood count showed a white blood cell count (WBC) of 126K/µL, hemoglobin of 16.7g/dL, platelet count of 23K/µL, and 47% circulating lymphoblasts (Fig. 1A).