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Recent findings in leukemia provide new insights

04-20-2006

Study 1: Nucleophosmin (NPM1) gene mutations predicted favorable prognosis in acute myelogenous leukemia (AML) with a normal karyotype.

According to a study from Germany, "NPM1 exon-12 gene mutations are the hallmark of a large AML subgroup with normal karyotype, but their prognostic value in this AML subset has not yet been determined. We screened 401 AML patients with normal karyotype treated within the German AML Cooperative Group Protocol 99 (AMLCG99) study for NPM1 mutations."

"Results were related with partial tandem duplications within the MLL gene (MLL-PTD), Fms-like tyrosine kinase 3-length mutations (FLT3-LM), the tyrosine kinase domain of FLT3 (FLT3-TKD), NRAS, KIT, and CEBPA mutations and with clinical characteristics and outcome. NPM1 mutations were detected in 212 (52.9%) of 401 patients. Fourteen mutations, including 8 new variants, were identified," explained S. Schnittger and colleagues, University Hospital Grosshadern.

"NPM1-mutated cases associated frequently with FLT3 mutations but rarely with other mutations. The NPM1-mutated group had a higher complete remission (CR) rate (70.5% vs 54.7%, p=.003), a trend to a longer overall survival (OS; median 1012 vs 549 days, p=.076), and significantly longer event-free survival (EFS; median 428 vs 336 days; p=.012). The favorable impact of NPM1 mutations on OS and EFS clearly emerged in the large group (264 [66.8%] of 395 cases) of normal-karyotype AML without FLT3-LM. This positive effect was lost in the presence of a concomitant FLT3-LM, since survival of the NPM1+/FLT3-LM+ double positive was similar to NPM1-/FLT3-LM+ cases."

The researchers concluded, "This study demonstrates that NPM1+/FLT3-LM- mutations are an independent predictor for a favorable outcome in AML with normal karyotype."

Schnittger and colleagues published the results of their research in Blood (Nucleophosmin gene mutations are predictors of favorable prognosis in acute myelogenous leukemia with a normal karyotype. Blood, 2005;106(12):3733-3739).

For additional information, contact S. Schnittger, University Hospital Grosshadern, Munich, Germany.

Study 2: Nucleophosmin (NPM) mutations were found in childhood acute myelogenous leukemia (AML) with normal karyotype.

"NPM is a nucleocytoplasmic shuttling protein involved in leukemia-associated chromosomal translocations, and it regulates the alternate reading frame (ARF)-p53 tumor-suppressor pathway. Recently, it has been demonstrated that mutations of the NPM1 gene alter the protein at its C-terminal, causing its cytoplasmic localization," researchers in Italy reported.

"Cytoplasmic NPM was detected in 35% of adult patients with primary non-French-American-British (FAB) classification M3 AML, associated mainly with normal karyotype," explained G. Cazzaniga and colleagues, University of Milano Bicocca.

"We evaluated the prevalence of the NPM1 gene mutation in non-M3 childhood AML patients enrolled in the ongoing Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP-AML02) protocol in Italy. NPM1 mutations were found in 7 (6.5%) of 107 successfully analyzed patients. NPM1-mutated patients carried a normal karyotype (7/26, 27.1%) and were older in age."

The researchers concluded, "Thus, the NPM1 mutation is a frequent abnormality in AML patients without known genetic marker; the mutation may represent a new target to monitor minimal residual disease in AML and a potential candidate for alternative and targeted treatments."

Cazzaniga and colleagues published their study in Blood (Nucleophosmin mutations in childhood acute myelogenous leukemia with normal karyotype. Blood, 2005;106(4):1419-1422).

For additional information, contact A. Biondi, University of Milano Bicocca, Ospedale San Gerardo, M Tettamanti Research Center, Pediatrics Clinic, I-20052 Monza, Italy.

Study 3: Acute myelogenous leukemia (AML) with tetrasomy 8 was associated with a poor prognosis.

According to recent research from Greece, "Tetrasomy 8 is an extremely rare chromosome abnormality, one that has been reported in only a few cases with myeloid malignancies. The majority of reported cases consist of AML of monocytic lineage."

"In slightly more than half of the patients, tetrasomy 8 was the single cytogenetic abnormality. Fluorescence in situ hybridization revealed tetrasomy 8 and trisomy 8 concurrently in all but one of the bone marrow samples. The clonal relationship between trisomy 8 and tetrasomy 8 in these cases remains to be clarified. Patients with tetrasomy 8 have a poor prognosis, and only 1 out of 33 patients was free of disease 3 years after autologous bone marrow transplantation," explained P. Tsirigotis and colleagues, University of Athens.

The researchers concluded, "Here, we report the case of a 25-year-old female patient with monocytic leukemia and tetrasomy 8."

Tsirigotis and colleagues published their study in Cancer Genetics and Cytogenetics (Acute myelogenous leukemia with tetrasomy 8 is a disease with a poor prognosis. Cancer Genet Cytogenet, 2005;161(1):78-81).

For additional information, contact P. Tsirigotis, University of Athens, Attikon Hospital, Hematology Unit, Dept. Internal Medicine 2, 1 Rimini St., Haidari 12462, Greece.

Keywords: Haidari, Greece, Bone Marrow, Cancer Genetics, Diagnosis, Diagnostics, Genetics, Leukemia, Oncology, Acute Myelogenous Leukemia, Tetrasomy 8.

This article was prepared by Cancer Weekly editors from staff and other reports. Copyright 2006, Cancer Weekly via NewsRx.com.